To Kill a Mockingbird author Harper Lee is back in court.
Only weeks ago, the 87-year-old writer settled a dispute with her former agent over an alleged "scheme to dupe" her into assigning the valuable copyright to her book. Now, she's alleging that a museum in her hometown of Monroe County, Ala., is exploiting her trademark and personality rights.
The lawsuit filed in Alabama federal court targets the Monroe County Heritage Museum.
According to the complaint, "The town’s desire to capitalize upon the fame of To Kill a Mockingbird is unmistakable: Monroeville’s town logo features an image of a mockingbird and the cupola of the Old County Courthouse, which was the setting for the dramatic trial in To Kill a Mockingbird."
The museum is reported to have generated more than $500,000 in revenue in 2011, and Lee objects to claims made in IRS documents that its mission is "historical."
"Its actual work does not touch upon history," says the lawsuit. "Rather, its primary mission is to trade upon the fictional story, settings and characters that Harper Lee created in To Kill a Mockingbird, and Harper Lee's own renown as one of the nation's most celebrated authors."
It's not often that a celebrity picks a legal war over a hometown institution that aims to profit on the back of a local icon. "Historical facts belong to the world," notes the lawsuit, "but fiction and trademarks are protected by law."
In Lee's 1960 book, the small-town lawyer character Atticus Finch defends an African-American man accused of rape. Among the alleged unauthorized uses of her trademark is the way the museum is advertising its venue: "Restored to its 1930s appearance, our courtroom is the model for Harper Lee’s fictional courtroom settings in To Kill a Mockingbird. It’s now one of the most recognized courtrooms in America because of the popular film version of the book.”
The museum (website: tokillamockingbird.com) is said to be selling aprons, T-shirts, fleece vests, onesies, hand towels, soaps, wine bags, magnets, glassware, bookmarks, beverage huggers and more.
Lee stops short of saying she's selling any of these commercial items herself. But she leaves open the possibility. According to the complaint (read in full here), "It was likely that, when Defendant began its use of the words, terms and name 'To Kill a Mockingbird' and 'Harper Lee,' long after Plaintiff’s marks and names had become famous, that the Plaintiff was already likely to enter those fields."
The author has attempted trademark registrations on To Kill a Mockingbird, and has been opposed by the Monroe County Heritage Museum. Lee says the attempts to cancel her trademark have been made in "bad faith" and goes so far as to claim that "Defendant knowingly withheld material information from the [Trademark Trials and Appeals] Board that it had made material statements to Plaintiff and to third parties that are inconsistent with the Defendant’s claim of senior rights in the mark."
Lee also accuses the museum and its attorney of lying to the media. After a Reuters article appeared about the fight at the trademark office, the museum's lawyer is alleged to have pushed for a correction to make clear it was not refusing to share profits with Lee.
"The correction was incorrect," says the lawsuit. "In correspondence dated June 6, 2013, Defendant’s counsel demanded a 'royalty-free' license as a condition of not opposing Ms. Lee’s application for registration of her trademark and on August 1, 2013 refused Ms. Lee’s offer to sell authorized merchandise to Defendant. The Defendant steadfastly refused, saying that 'the museum is not going to purchase its TKAM merchandise from Ms. Lee'; it falsely denied this behavior when asked about it by the press."
Lee won't be denied satisfaction in court just because of her age.
"Ms. Lee suffered a stroke and is in ill health," says the lawsuit. "The Defendant apparently believes that she lacks the desire to police her trademarks, and therefore seeks to take advantage of Ms. Lee’s condition and property. The Defendant is mistaken."
"I have not read it and not been served," says Stephanie Rogers, the museum's executive director. "The museum has been doing what we always have done. We honor her here. We don't sell anything with her name. We sell memorabilia to those who come to see a production of 'To Kill a Mockingbird' that we secure dramatic rights to. Everything we do is above board. I'm shocked by this."
Itching for a better smartphone camera, but can't afford to buy an unlocked device? You're in luck: Samsung's Galaxy S4 Zoom appears to be coming to AT&T. Images of the AT&T branded smart camera (complete with carrier identification and official apps) appeared on Twitter today, hinting that a AT&T subsidized version of the device could be forthcoming. The 16-megapixel Zoom is an intriguing mash up between the Galaxy Camera and the Galaxy S4 Mini, but unless Ma Bell has made some major tweaks to the device, we wouldn't run out to your local AT&T store: the original was kind of a mess.
The team at Gogo is flying high lately both in the sky and on the ground thanks to its new hybrid GTO technology, which brings in-air download speeds up to 60 Mbps. To test the future of in-flight WiFi, Gogo uses the "Gogo One," a flying laboratory that comes outfitted with some pretty intense ...
Hikers and campers can now keep their cameras charged with FlameStower, which uses heat from a campfire, stove or even candles to charge any device powered by a USB connection. While this can seem superfluous — powering up while getting away from it all — creators Andrew Byrnes and Adam Kell says the device can also bring power to people in developing countries where wireless technology has leapfrogged others, places where people have cellphones but not electricity.
Byrnes and Kell were both studying materials science at Stanford University and at first thought about a generator wired to a toaster, but they quickly dismissed that idea. They spoke to a business school professor, who told them something that's been their guiding principle since — build something that can cook a pot of rice and charge a cellphone at the same time.
The technology is fairly simple. The FlameStower has a blade that extends out over the fire, while the other end is cooled by a reservoir of water. That means one part of the blade is hotter than the other. The temperature difference generates electricity, and semiconductors amplify the voltage to a useful amount. It gives you the same charge as connecting your phone to a laptop. The Mars Curiosity Rover uses the same technology, though its heat source comes from decaying radioactive materials.
This phenomenon of heat to electricity is called the Seebeck effect, and it doesn't generate a lot of energy, which means it wasn't that useful until people started walking around with cameras and smartphones.
"Now you have these tools that are insanely powerful, and increasingly are stingy on their energy use, so that value of the low amount of electricity is getting higher," Byrnes says.
He and Kell want to bring the FlameStower not only to stores in the U.S. but to developing countries as well. Kell recently returned from a trip to rural Kenya and Ethiopia to refine the FlameStower for users there, because around 65 percent of people in Africa have cellphones, but only 42 percent have electricity.
"[The cellphone] has been the first technology that people in rural villages are actually buying," Kell says.
Kell says products sold in developing countries are usually made to be cheaper than their counterparts in the U.S., with the exception of energy, which is much more expensive and less reliable.
Kell and Byrnes aren't the only people to come up with something like this. The BioLite CampStove and PowerPot are both pots that will charge a device and cook your food or boil water at the same time. But Kell says they weren't as successful in developing countries because people there often want to use their own pots, so the FlameStower founders made something that can work on any stove or fire.
At the moment a FlameStower costs $80, and the project is being funded on Kickstarter until late October.
BERLIN (Reuters) - Germany's Greens ruled out any further coalition talks with Angela Merkel's conservatives early on Wednesday, leaving the chancellor to focus on discussions with the center-left Social Democrats (SPD) in her efforts to form a new government.
After almost six hours of detailed policy discussions the Greens concluded they simply did not have enough in common with Merkel's conservative bloc in areas such as energy, climate targets and taxation, to make further discussions fruitful.
"After these talks the Greens do not find themselves able to enter coalition talks," said Hermann Groehe, second-in-command of Merkel's Christian Democrats (CDU).
"We will approach the representatives of the SPD tomorrow with a view to scheduling the explorative talks we had already eyed for Thursday."
Merkel needs to find a partner for her third term after she won September's election but fell short of an absolute majority. Polls suggest the German public would like her to enter full-blown negotiations with the SPD, and aim for a repeat of the 'grand coalition' in which she governed from 2005-2009.
The SPD, however, are playing hard to get. Its representatives spoke to the CDU and its Bavarian sister party, the Christian Social Union (CSU), for eight hours on Monday, and while stating their willingness to talk again, they also said they could also say no to Merkel.
The prospect of months of coalition talks worries Germany's European partners, who fear delays to crucial decisions for fighting the euro zone crisis, such as a plan for banking union.
An eventual grand coalition is expected to boost spending on investment in Germany, helping shore up Europe's largest economy and increasing trade with the struggling euro zone, helping address imbalances.
Although the CDU/CSU and Greens were ultimately unable to bridge differences, the fact that the former arch-enemies spoke at all and for so long is already groundbreaking and signals a new political culture in Germany.
"I want to stress that even in areas where there were differences, there were none which we would have viewed as insurmountable," said Groehe.
However, taxation appeared a major stumbling block, with the Greens anxious to fund an ambitious investment program.
Former Greens co-chair Claudia Roth said: "We always said it was about seeing whether there was a solid foundation for four years of government together - and after these talks it appears there wasn't."
The policy divide with the SPD looks to be smaller.
The SPD has already signaled it could stop insisting on tax hikes if Merkel's camp can come up with other ways to pay for more investment in infrastructure, education and research, which all the mainstream parties agree is necessary.
The big sticking point is a minimum wage. In the talks on Monday, the SPD made clear it would not compromise on its demand for a nationwide wage floor of 8.50 euros per hour.
But even here, the divide between the parties is more about method than substance. Merkel agrees in principle to the idea of a wage floor, but wants this to be negotiated sector by sector, rather than imposed from above.
On a range of other issues, from how to tackle Europe's economic and financial woes to completing Germany's shift from nuclear to renewable energy, the differences are minimal.
Still, the path to an eventual grand coalition won't be smooth.
SPD leaders must take care not to appear overly eager for a deal with Merkel given deep skepticism among the party's rank and file. On Sunday, 200 senior SPD members will vote on whether to continue coalition talks, and any final decision on forming a new government will be put to a vote by the party's 472,000 members.
(Reporting by Andreas Rinke and Hans Edzard Buseman; Writing by Alexandra Hudson; Editing by Annika Breidthardt and Paul Simao)
20th Century Fox announced that Son of God, the film based on History Channel's miniseries The Bible, will open wide in U.S. theaters on Feb. 28, 2014.
The 10-hour miniseries The Bible, produced by husband-and-wife team Mark Burnett and Roma Downey, was a breakout hit for History, garnering an average of 15 million viewers per episode. It also earned three Emmy nominations.
The big-screen treatment will follow Christ from his birth through his crucifixion and resurrection.
Portuguese actor DiogoMorgado is starring. The film will feature selections from the miniseries plus additional scenes that were left on the cutting room floor. Hans Zimmer created the score.
"We are very excited to be working with 20th Century Fox to release Son of God as a major motion picture," said Downey and Burnett in a statement. "We responded to an overwhelming demand for the greatest story ever told to be seen as a shared experience on the big screen. The result is a beautiful stand-alone movie. It's the story of Jesus for a whole new generation."
Son of God will go up against two other wide releases on Feb. 28. Universal's airplane thriller Non-Stop starring Liam Neeson and Paramount's sci-fi thriller Almanac, which centers around a time machine, also open on that date.
WASHINGTON (Reuters) - The White House dismissed the latest fiscal proposal offered by Republicans who control the House of Representatives on Tuesday, calling it a partisan attempt to appease a small group of Tea Party conservatives.
With time running out toward a Thursday deadline to avert a historic U.S. debt default, House Speaker John Boehner, the top Republican in Washington, proposed an alternative to a Senate plan that would affect Obama's signature healthcare law.
White House spokesman Amy Brundage said Obama has vowed repeatedly that lawmakers "don't get to demand ransom for fulfilling their basic responsibilities to pass a budget and pay the nation's bills."
"Unfortunately, the latest proposal from House Republicans does just that in a partisan attempt to appease a small group of Tea Party Republicans who forced the government shutdown in the first place," she said.
Brundage said Democrats and Republicans in the Senate have been working in a good-faith effort to end the fiscal stalemate and "it's time for the House to do the same."
(Reporting By Roberta Rampton and Steve Holland; editing by Christopher Wilson)
A key al-Qaeda planner indicted for bombings of American embassies in Kenya and Tanzaniahas been brought to American soil for medical treatment, sparking outrage by some who say he should have been sent to Guantanamo Bay. NBC's Richard Engel reports.
FBI via AP
By Erin McClam, Staff Writer, NBC News
A suspected al Qaeda operative captured by U.S. special forces in Libya is due in federal court in New York on Tuesday to face charges that he helped plan the 1998 bombings of two American embassies in Africa.
The suspected operative, Abu Anas al-Libi, was whisked off the streets of Tripoli on Oct. 5 and held aboard the USS San Antonio, where he was locked in the brig and questioned without Miranda rights, U.S. officials said.
Because of what U.S. officials have described as a serious medical condition — his family says it is severe hepatitis — he was taken within a week to New York, where he has been under indictment since 1998.
Some Republicans in Congress said that he should have been sent to the U.S. prison at Guantanamo Bay, Cuba, for further interrogation.
“This isn’t a question of getting a conviction,” said Rep. Peter King, R-N.Y. “It was a question of getting intelligence.”
He is one of 21 men indicted in the bombings of the American embassies in Kenya and Tanzania, which killed more than 200 people. He is among nine in custody. Eight have been killed, including Osama bin Laden; one died awaiting trial, and three are at large.
The indictment accuses al-Libi of helping plan the attacks and of conducting surveillance of the embassy and other diplomatic facilities in Nairobi, Kenya.
According to testimony at an earlier embassy bombing trial, it was al-Libi, who was in London at the time of the attacks, who first proposed the bombing of foreign embassies in 1993.
Richard Engel of NBC News contributed to this report.
Related:
Fugitive al Qaeda leader was hardly lying low in Libya, photos show
Slow-motion manhunt: U.S. relentlessly pursues '98 embassy bombing suspects
This story was originally published on Tue Oct 15, 2013 10:38 AM EDT
Quirky singer Ke$ha made an appearance on “Jimmy Kimmel Live” and talked about her past lives and having a ghost exorcised from her va-jay-jay.
The singer showed off her newly-trim body and killer legs, rocking newly multi-color locks!
Last night Ke$ha told Jimmy Kimmel about the treacherous conditions she endured on her way to his show from Alaska, sharing a video of herself in a boat in really nasty weather.
Ke$ha debuted cotton candy-colored hair as she told the talk show host some crazy stuff.
The singer talked about hypnotherapy and how she lived past lives as a warrior and as a “cool” man. She is known for saying and doing outlandish things but seems to really believe them.
Ke$ha said her hypnotherapist revealed she had dead people in her body, with a ghost-meter alerting them to problems in her private area. Ke$ha said she believes that was caused by her “going through a dry spell”.
Jimmy Kimmel asked Ke$ha about her recent sexy photos posted online and she claimed she was just bored and had cabin fever.
Ke$ha’s tour with Pitbull’s Australian tour was recently canceled just weeks before they were to perform.
The singer tweeted, “Im so so bummed that our aussie tour was cancelled!! aussie animals, i love you very much and im working out how to come see you again asap”.
The second-largest hospital in the Southern African country of Swaziland may be operating a black market in human body parts used in magic spells, according to claims made by a reverend and others.
The organ trade at Raleigh Fitkin Memorial Hospital in the city of Manzini has been described as "an open secret" by critics such as Rev. Grace Masilela. Accusers say people come to the hospital from neighboring South Africa to buy bones, hearts, brains and other organs.
Whether or not this particular claim is true, such a practice is not uncommon in the area. There, traditional healers or witch doctors often grind up body parts and combine them with roots, herbs, seawater, animal parts and other ingredients to prepare potions and spells for their clients. Sometimes clients eat the mixture or rub it on the skin or into open wounds. In the region, the practice of using body parts for magical ritual or benefit is called "muti," a Zulu word meaning "medicine." [15 Crazy Urban Legends Debunked]
Magical beliefs
Belief in magic is widespread throughout Sub-Saharan Africa, according to a 2010 Gallup poll in which over half of the respondents reported personally believing in witchcraft and magic.
"Setbacks or calamities, such as drought or illness, are signs that the natural and social order have been disturbed. One means of obtaining this extra portion of luck or restoring the natural order is through the use of strong muti. It is with this strong muti that muti murders are often associated. Muti made from human body parts is considered to be exceptionally powerful."
Muti murders differ from ritual or sacrificial killings in that the goal is not necessarily to kill the victim (though that often happens due to shock and blood loss), but instead to obtain body parts.
Just as different ingredients in a recipe are used for different purposes, certain body parts are used for particular goals. For example, eyes may be stolen and used in a magic ritual to help restore a client's failing eyesight, whereas severed hands are used to assure business success, and genitals are believed to attract luck. [The Surprising Origins of 9 Common Superstitions]
In some cases, criminals have been arrested during robberies with muti in their pockets, having been told by a healer that the medicine from such body parts would make the thieves invisible to police — or even bulletproof.
Fresh body parts needed
Body parts from live victims are said to be the most powerful, though organs taken from the dead are sometimes used, as is claimed to have happened in Swaziland. Labuschagne notes, "There seems to be an increase in grave robbing, where the body parts removed are similar to those used in muti. Also, theft or sale of body parts from hospitals and mortuaries has occurred. It is uncertain whether or not the traditional healer would be able to tell if a body part is removed pre- or post-mortem."
Stealing organs from the dead for use in magic spells is a ghastly crime, but at least the unwilling donors are deceased. Just as often, murderers working on behalf of witch doctors attack and kill innocent people for their body parts. Muti murders are particularly brutal, with knives, machetes or even glass shards used to cut and hack off limbs, breasts and other body parts from their victims, including children.
In East Africa, at least 50 albinos were murdered for their body parts in 2009, according to the Red Cross. An albino's' arms, fingers, genitals, ears and blood are highly prized for their especially powerful magic, according to believers.
Muti murders have occurred throughout South Africa, and especially in rural areas. Reliable figures on the number of muti murders in the country are elusive, because police do not track those murders separately from other homicides. Even so, estimates range from a few dozen to a few hundred murders per year.
Science fiction fans may recall that muti was featured in the hit South African film "District 9," in which a local warlord tries to steal the hero's body parts, believing the stolen limbs would give him magical powers.
Most Africans, and most traditional healers there, reject muti murder and don't engage in the practice. Still, the belief that body parts can aid in magic rituals has been a part of African culture for centuries, and it will likely remain so.
Benjamin Radford is deputy editor of "Skeptical Inquirer" science magazine and author of six books including "The Martians Have Landed! A History of Media Panics and Hoaxes." His Web site is www.BenjaminRadford.com.
Follow us @livescience, Facebook & Google+. Original article on LiveScience.
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Just as in the cosmological model that explains how the universe sprang into existence from an infinitely dense singularity, CBS’ The Big Bang Theory has grown with such explosive force that it appears to be its own ever-expanding universe.
According to media buyers surveyed byAdweek, The Big Bang Theory in its seventh season now commands a staggering $326,260 per 30-second spot, topping the likes of NBC’s TheVoice ($264,575 for the higher-rated Wednesday night show), ABC’s ModernFamily ($257,435) and Fox’s The Simpsons ($256,963).
The robust unit cost is a function of BigBang’s monster ratings—three episodes into the fall season, Chuck Lorre’s sitcom is averaging 19.2 million viewers and a 5.6 rating in the adults 18-49 demo—and its seemingly unstoppable growth. After posting full-season highs two years running, Big Bang’s ratings are currently trending up 12 percent versus the 2012-13 campaign.
While the NFL commands the highest unit cost of any TV property—Fox’s roster of eight late national NFC games fetches a jaw-dropping $595,000 per :30, while each unit in NBC’s Sunday Night Football franchise is worth around $570,000 a throw—the general entertainment programs enjoy a longer run: 35 weeks when lower-priced repeats are factored in.
Among the Big Four broadcast nets, CBS earns the biggest average premiums for its freshman series. The Crazy Ones, the new Tuesday 9 p.m. anchor starring RobinWilliams as an idiosyncratic ad agency boss, boasts an average unit cost of $175,200—the highest rate for any new comedy. The defending ratings champ also earns top dollar for Big Bang lead-out The Millers ($122,390), Lorre’s latest multicamera sitcom Mom ($138,575) and the ratings-challenged serialized thriller Hostages ($134,420).
ABC’s established reach vehicles (Modern Family, Grey’s Anatomy and, more recently, Scandal) and its popularity with younger, affluent women have allowed it to remain competitive despite ongoing ratings hiccups. But it’s a new male-skewing series that’s really leading the charge this fall, as Marvel’s Agents of S.H.I.E.L.D. is pricing at an average rate of $169,730 per :30. Lead-out comedies The Goldbergs ($93,200) and Trophy Wife ($91,175) are roughly on par with the former time slot occupants, while the canceled lottery drama Lucky 7 was a bad bet at $86,355 a pop.
ABC’s new Rebel Wilson sitcom Super Fun Night is fetching around $130,823 for each 30-second spot, an increase of some 33 percent compared to its predecessor, The Neighbors.
Having inherited the plum Voice lead-out from Revolution, NBC’s The Blacklist enjoys the distinction of being the most valuable new series on the dial ($198,667). And while that has helped establish NBC as the most expensive environment on Monday nights, pricing parity hasn’t trickled down to new shows like Ironside ($71,500) and Welcome to the Family ($62,370). That said, The Michael J. Fox Show commands a healthy $110,050 per spot.
Fox’s lighter load of newbies includes broadcast’s best new bargain (Sleepy Hollow, $139,120), the underperforming Dads ($120,100) and the on-the-bubble AndySamberg comedy Brooklyn Nine-Nine ($96,225).
A photo released by NASA this summer shows a photo composed of nearly 900 images taken by the rover Curiosity, showing a section of Gale Crater near the equator of Mars. The rovers are continuing to work through the U.S. government shutdown.
NASA/AP
A photo released by NASA this summer shows a photo composed of nearly 900 images taken by the rover Curiosity, showing a section of Gale Crater near the equator of Mars. The rovers are continuing to work through the U.S. government shutdown.
NASA/AP
The budget negotiations in Washington are not front-page news on Mars. There, millions of miles away, NASA's rovers continue to operate, taking photographs and collecting data as they prepare for the coming Martian winter.
NPR's Joe Palca has this report for our Newscast unit:
"NASA's newest rover, called Curiosity, is on the move. It's headed to the base of Mount Sharp, a mountain that towers three-and-a-half miles above the floor of Gale crater where the rover landed. Scientists hope the foothills of the mountain will reveal some of the ancient geologic history of Mars.
"The other rover called Opportunity is studying something similar at the rim of Endeavor crater. In January, the rover that was designed to last 90 days will mark its tenth year on Mars.
"Some of Opportunity's instruments have stopped working, but it's still taking pictures and still roves across the surface, albeit quite a but slower than its newer partner on the other side of the planet."
The two rovers are taking in data and getting into strategic locations before winter arrives on Mars in a few months.
The scarcity of sunlight shouldn't pose a challenge for Curiosity, whose systems are powered by heat generated by the radioactive decay of plutonium. NASA hopes that the older Opportunity, which powers itself with solar panels, will be aided by its position on a north-facing slope.
As the Planetary Society website notes, this will be Opportunity's sixth winter:
"Harsh beyond belief, winters on Mars are life threatening, even for robots. Opportunity must endure constant, sometimes radical fluctuations in daily temperatures, not to mention survive temperatures as low as 100 degrees below freezing, all of which is really tough on her metal parts. Of course, the veteran rover has proved its resilience many times over while exploring this sub-freezing planet."
The Cancer Genome Atlas exposes more secrets of lethal brain tumor
Public release date: 10-Oct-2013 [
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Contact: Scott Merville smerville@mdanderson.org 713-792-0661 University of Texas M. D. Anderson Cancer Center
Project delves deeply into genomics of 599 glioblastoma multiforme cases to better target disease
HOUSTON When The Cancer Genome Atlas launched its massively collaborative approach to organ-by-organ genomic analysis of cancers, the brain had both the benefit, and the challenge, of going first.
TCGA ganged up on glioblastoma multiforme (GBM), the most common and lethal of brain tumors, with more than 100 scientists from 14 institutions tracking down the genomic abnormalities that drive GBM.
Five years later, older and wiser, TCGA revisited glioblastoma, producing a broader, deeper picture of the drivers and potential therapeutic targets of the disease published in the Oct. 10 issue of Cell.
"The first paper in 2008 characterized glioblastoma in important new ways and illuminated the path for all TCGA organ studies that have followed," said senior author Lynda Chin, M.D., professor and chair of Genomic Medicine and scientific director of the Institute for Applied Cancer Science at The University of Texas MD Anderson Cancer Center.
"Our new study reflects major improvements in technology applied to many more tumor samples to more completely characterize the landscape of genomic alterations in glioblastoma," said Chin, who was also co-senior author of the first paper while she was on the faculty of Dana-Farber Cancer Institute in Boston.
"Information generated by this unbiased, data-driven analysis presents new opportunities to discover genomics-based biomarkers, understand disease mechanisms and generate new hypotheses to develop better, targeted therapies," Chin said.
About 23,000 new cases of GBM are predicted in the United States during 2013 and more than 14,000 people expected to die of the disease. Most patients die within 15 months of diagnosis.
Well of rich, detailed data will nurture better treatment
New information about genetic mutations, deletions and amplifications; gene expression and epigenetic regulation; structural changes due to chromosomal alterations, proteomic effects and the molecular networks that drive GBM make for a deep, broad dataset that will underpin research and clinical advances for years to come.
"Our main contribution is this tremendous resource for the GBM research community, which is already heavily relying on the earlier TCGA study," said co-lead author Roeland Verhaak, Ph.D., assistant professor of Bioinformatics and Computational Biology at MD Anderson. "Whatever new treatments people come up with for GBM, I'm very confident that their discovery and development will in some way have benefited from this rich and detailed data set," he said.
The Cell paper describes analysis of tumor samples and molecular data from 599 patients at 17 study sites. Detailed clinical information including treatment and survival was available for almost all cases.
New targetable mutations
In addition to confirming significantly mutated genes discovered earlier, such as the tumor suppressors TP53, PTEN and RB1 and the oncogene PIK3CA, the analysis identified 61 new mutated genes. The most frequent mutations occurred in from 1.7 to 9 percent of cases.
Two of these, BRAF and FGFR, might have more immediate clinical relevance, Verhaak noted. MD Anderson neuro-oncologists are checking to see if patients have these mutations. Drugs are available to address those variations now, Verhaak said. The BRAF point mutation in GBM is the same commonly found in melanoma, which is treated by a new class of drugs.
More twists and turns for EGFR
The larger data set and an improved analytical algorithm allowed major refinement of gene amplification and deletion information. For example, common amplification events were found to occur more frequently than previously known, including amplification of the epidermal growth factor receptor (EGFR) on chromosome 7.
EGFR is both amplified and mutated frequently in GBM; yet therapeutic efforts targeting EGFR so far have failed. "We found EGFR is more frequently altered than we already thought," Verhaak said.
Overall, the EGFR gene was mutated, rearranged, amplified or otherwise altered in 57 percent of tumors. Increased EGFR protein levels in GBM cells correlated with the many mechanisms of EGFR alteration, Verhaak said.
A treatment based on EGFR still has great potential, he noted. But strategies to target EGFR will need to address the likelihood that different alterations of EGFR might be present in the same tumor and affect the impact of targeted drugs.
Breaking GBM into molecular subtypes
Verhaak and other researchers in recent years have begun to classify GBM tumors by gene expression. Four such subgroups -- neural, proneural, mesenchymal and classical -- were further characterized by DNA methylation pattern, signaling pathway activity and by clinical measures such as survival and treatment response. Methylation of a gene turns it off.
Understanding the subgroups could establish biomarkers to guide treatment and identify new therapeutic targets.
The team found, for example, that the survival advantage of the proneural subtype depends on a specific DNA methylation pattern known as G-CIMP and that DNA methylation of the MGMT gene may serve as a biomarker of treatment response in the classical subtype.
###
Co-authors with Chin and Verhaak are 56 investigators from 39 institutions on behalf of the TCGA Research Network. MD Anderson co-authors are Siyuan Zheng, Ph.D., Rahulsimham Vegesna, and John Weinstein, M.D., Ph.D., of Bioinformatics and Computational Biology; W.K. Yung, M.D., of Neuro-Oncology; Kenneth Aldape, M.D., and Wei Zhang, Ph.D., of Pathology and Gordon Mills, M.D., Ph.D., of Systems Biology.
Zhang, Weinstein and Chin are all leaders or co-leaders of three of the seven TCGA Genome Analysis Centers.
Co-lead authors with Verhaak are Cameron Brennan, M.D., of Memorial Sloan-Kettering Cancer Center in New York and Aaron McKenna, Ph.D., of the Broad Institute of Harvard and MIT.
TCGA is a joint project of the National Cancer Institute and the National Human Genome Research Institute of the National Institutes of Health. This glioblastoma project was funded by NIH grants (U24CA143883, U24CA143858, U24CA143840, U24CA143799, U24CA143835,
U24CA143845, U24CA143882, U24CA143867, U24CA143866, U24CA143848, U24CA144025, U24CA143843, U54HG003067, U54HG003079, U54HG003273, U24CA126599, U24CA126544, U24CA126546, U24CA126551, U24CA126554, U24CA126561, U24CA126563, U24CA143731, U24CA143843.)
About UT MD Anderson Cancer Center
The University of Texas MD Anderson Cancer Center in Houston ranks as one of the world's most respected centers focused on cancer patient care, research, education and prevention. MD Anderson is one of only 41 comprehensive cancer centers designated by the National Cancer Institute. For 10 of the past 12 years, including 2013, MD Anderson has ranked No. 1 in cancer care in U.S. News & World Report's annual "Best Hospitals" survey. MD Anderson receives a cancer center support grant from the National Cancer Institute of the National Institutes of Health (P30 CA016672).
Get MD Anderson News Via RSS Follow MD Anderson News on Twitter
Contact:
Scott Merville External Communications 713-792-0611 office 713-515-4855 mobile smerville@mdanderson.org
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The Cancer Genome Atlas exposes more secrets of lethal brain tumor
Public release date: 10-Oct-2013 [
| E-mail
| Share
]
Contact: Scott Merville smerville@mdanderson.org 713-792-0661 University of Texas M. D. Anderson Cancer Center
Project delves deeply into genomics of 599 glioblastoma multiforme cases to better target disease
HOUSTON When The Cancer Genome Atlas launched its massively collaborative approach to organ-by-organ genomic analysis of cancers, the brain had both the benefit, and the challenge, of going first.
TCGA ganged up on glioblastoma multiforme (GBM), the most common and lethal of brain tumors, with more than 100 scientists from 14 institutions tracking down the genomic abnormalities that drive GBM.
Five years later, older and wiser, TCGA revisited glioblastoma, producing a broader, deeper picture of the drivers and potential therapeutic targets of the disease published in the Oct. 10 issue of Cell.
"The first paper in 2008 characterized glioblastoma in important new ways and illuminated the path for all TCGA organ studies that have followed," said senior author Lynda Chin, M.D., professor and chair of Genomic Medicine and scientific director of the Institute for Applied Cancer Science at The University of Texas MD Anderson Cancer Center.
"Our new study reflects major improvements in technology applied to many more tumor samples to more completely characterize the landscape of genomic alterations in glioblastoma," said Chin, who was also co-senior author of the first paper while she was on the faculty of Dana-Farber Cancer Institute in Boston.
"Information generated by this unbiased, data-driven analysis presents new opportunities to discover genomics-based biomarkers, understand disease mechanisms and generate new hypotheses to develop better, targeted therapies," Chin said.
About 23,000 new cases of GBM are predicted in the United States during 2013 and more than 14,000 people expected to die of the disease. Most patients die within 15 months of diagnosis.
Well of rich, detailed data will nurture better treatment
New information about genetic mutations, deletions and amplifications; gene expression and epigenetic regulation; structural changes due to chromosomal alterations, proteomic effects and the molecular networks that drive GBM make for a deep, broad dataset that will underpin research and clinical advances for years to come.
"Our main contribution is this tremendous resource for the GBM research community, which is already heavily relying on the earlier TCGA study," said co-lead author Roeland Verhaak, Ph.D., assistant professor of Bioinformatics and Computational Biology at MD Anderson. "Whatever new treatments people come up with for GBM, I'm very confident that their discovery and development will in some way have benefited from this rich and detailed data set," he said.
The Cell paper describes analysis of tumor samples and molecular data from 599 patients at 17 study sites. Detailed clinical information including treatment and survival was available for almost all cases.
New targetable mutations
In addition to confirming significantly mutated genes discovered earlier, such as the tumor suppressors TP53, PTEN and RB1 and the oncogene PIK3CA, the analysis identified 61 new mutated genes. The most frequent mutations occurred in from 1.7 to 9 percent of cases.
Two of these, BRAF and FGFR, might have more immediate clinical relevance, Verhaak noted. MD Anderson neuro-oncologists are checking to see if patients have these mutations. Drugs are available to address those variations now, Verhaak said. The BRAF point mutation in GBM is the same commonly found in melanoma, which is treated by a new class of drugs.
More twists and turns for EGFR
The larger data set and an improved analytical algorithm allowed major refinement of gene amplification and deletion information. For example, common amplification events were found to occur more frequently than previously known, including amplification of the epidermal growth factor receptor (EGFR) on chromosome 7.
EGFR is both amplified and mutated frequently in GBM; yet therapeutic efforts targeting EGFR so far have failed. "We found EGFR is more frequently altered than we already thought," Verhaak said.
Overall, the EGFR gene was mutated, rearranged, amplified or otherwise altered in 57 percent of tumors. Increased EGFR protein levels in GBM cells correlated with the many mechanisms of EGFR alteration, Verhaak said.
A treatment based on EGFR still has great potential, he noted. But strategies to target EGFR will need to address the likelihood that different alterations of EGFR might be present in the same tumor and affect the impact of targeted drugs.
Breaking GBM into molecular subtypes
Verhaak and other researchers in recent years have begun to classify GBM tumors by gene expression. Four such subgroups -- neural, proneural, mesenchymal and classical -- were further characterized by DNA methylation pattern, signaling pathway activity and by clinical measures such as survival and treatment response. Methylation of a gene turns it off.
Understanding the subgroups could establish biomarkers to guide treatment and identify new therapeutic targets.
The team found, for example, that the survival advantage of the proneural subtype depends on a specific DNA methylation pattern known as G-CIMP and that DNA methylation of the MGMT gene may serve as a biomarker of treatment response in the classical subtype.
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Co-authors with Chin and Verhaak are 56 investigators from 39 institutions on behalf of the TCGA Research Network. MD Anderson co-authors are Siyuan Zheng, Ph.D., Rahulsimham Vegesna, and John Weinstein, M.D., Ph.D., of Bioinformatics and Computational Biology; W.K. Yung, M.D., of Neuro-Oncology; Kenneth Aldape, M.D., and Wei Zhang, Ph.D., of Pathology and Gordon Mills, M.D., Ph.D., of Systems Biology.
Zhang, Weinstein and Chin are all leaders or co-leaders of three of the seven TCGA Genome Analysis Centers.
Co-lead authors with Verhaak are Cameron Brennan, M.D., of Memorial Sloan-Kettering Cancer Center in New York and Aaron McKenna, Ph.D., of the Broad Institute of Harvard and MIT.
TCGA is a joint project of the National Cancer Institute and the National Human Genome Research Institute of the National Institutes of Health. This glioblastoma project was funded by NIH grants (U24CA143883, U24CA143858, U24CA143840, U24CA143799, U24CA143835,
U24CA143845, U24CA143882, U24CA143867, U24CA143866, U24CA143848, U24CA144025, U24CA143843, U54HG003067, U54HG003079, U54HG003273, U24CA126599, U24CA126544, U24CA126546, U24CA126551, U24CA126554, U24CA126561, U24CA126563, U24CA143731, U24CA143843.)
About UT MD Anderson Cancer Center
The University of Texas MD Anderson Cancer Center in Houston ranks as one of the world's most respected centers focused on cancer patient care, research, education and prevention. MD Anderson is one of only 41 comprehensive cancer centers designated by the National Cancer Institute. For 10 of the past 12 years, including 2013, MD Anderson has ranked No. 1 in cancer care in U.S. News & World Report's annual "Best Hospitals" survey. MD Anderson receives a cancer center support grant from the National Cancer Institute of the National Institutes of Health (P30 CA016672).
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Contact:
Scott Merville External Communications 713-792-0611 office 713-515-4855 mobile smerville@mdanderson.org
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