PRESS-NEWS.org - Press Release Distribution
PRESS RELEASES DISTRIBUTION

Study finds molecular 'signature' for rapidly increasing form of esophageal cancer

2013-03-25
(Press-News.org) BOSTON—During the past 30 years, the number of patients with cancers that originate near the junction of the esophagus and stomach has increased approximately 600 percent in the United States. The first extensive probe of the DNA of these esophageal adenocarcinomas (EACs) has revealed that many share a distinctive mix-up of letters of the genetic code, and found more than 20 mutated genes that had not previously been linked to the disease. The research, led by scientists at Dana-Farber Cancer Institute, the Broad Institute, and other research centers, may offer clues to why EAC rates have risen so sharply. The findings, which are being released as an advanced online publication by Nature Genetics, point to an array of abnormal genes and proteins that may be lynchpins of EAC cell growth and therefore serve as targets for new therapies, according to the study's authors. "Adenocarcinomas of the esophagus, particularly those that arise at the gastroesophageal junction, were extremely uncommon 40 years ago and now account for approximately 15,000 new cases in the United States each year," said Adam Bass, MD, of Dana-Farber and the Broad Institute, who is co-senior author of the paper with Gad Getz, PhD, of the Broad Institute and Massachusetts General Hospital. "Unfortunately, it's also a disease with a generally poor prognosis: five years after diagnosis, only about 15 percent of patients are still alive. Bass added that despite the increased incidence of EAC, there have been few new approaches to treatment. "The goal of our study was to identify abnormalities within the genome of EAC cells to develop a foundation to better understand these tumors, diagnose them earlier, and develop better treatments," explained Bass. EAC is thought to be associated with chronic gastroesophageal reflux, which sends stomach acid gurgling into the esophagus. This produces a condition known as Barrett's esophagus, in which cells at the lower end of the esophagus change to resemble cells in the intestine. Patients with Barrett's esophagus often go on to develop EAC. Researchers don't know why EAC rates are increasing, but they speculate that it may be due to a rise in obesity, particularly in men: A heavier abdomen puts increased pressure on the stomach, causing acid to back up into the esophagus. In the new study, researchers "sequenced" specific sections of DNA in cells from 149 EAC tissue samples, reading the individual letters of the genetic code within those areas. They focused on the one percent of the genome that holds the codes for making cell proteins. They also sequenced the entire genome – all the DNA within the cell nucleus – of cells from 15 of these EAC samples. Prior to this study, the largest sequencing study of EAC involved only a dozen tumor samples. "We discovered a pattern of DNA changes that had not been seen before in any other cancer type," Getz remarked. The pattern involved a subtle swap in one of the four "nucleobases" that form the rungs of the DNA double helix, often designated by the letters C, T, G, and A. The investigators found that in many places where an A nucleobase was followed by another A nucleobase, the second "A" was replaced by a "C," a process known as transversion. "We found this type of transversion throughout the genomes of the EAC cells we analyzed," Bass stated. "Overall, about one-third of all the mutations we discovered within these cells involved this type of transversion. In some tumor samples, these transversions accounted for nearly half of all mutations," Getz added. Although A-to-C changes are not commonly observed in cancer, there is some evidence that oxidative damage can produce these changes. (Oxidative damage occurs when cells cannot neutralize the potentially harmful products of oxygen's reactions with other molecules.) "Gastric reflux can produce this type of damage, suggesting that reflux may underlie this pattern of mutations," Bass commented. In addition to the mutational "signature" of AA becoming AC, the research team identified 26 genes that were frequently mutated in the tumor samples. Five of these were "classic cancer genes" that had previously been implicated in EAC, Bass said, and the others were involved in a variety of cell processes. Among the genes not previously linked to EAC were ELMO1 and DOCK2, mutations that can switch on a gene called RAC1, which can cause cancer cells to invade surrounding tissue. "The discovery of mutated ELMO1 and DOCK2 in many of these tumors may indicate that this invasive process is particularly active in EAC, promoting metastasis," Bass related. "We know that EAC tumors tend to spread at an earlier stage than many other cancers, which may help explain why survival rates for EAC patients tend to be low." The RAC1 pathway – the network of genes that control RAC1 activity – is being pursued for pharmaceutical development. The discovery of ELMO1 and DOCK2 mutations in EAC samples may spur testing of new agents targeting this pathway in EAC, said Bass. "Identifying the mutated genes within these tumors will help us understand the underlying biology of the disease," said Bass. "It also presents us with a slate of known genetic abnormalities that can someday be used to diagnose the disease at an early stage, classify tumors by the particular mutations within EAC cells, and ultimately develop treatment geared to precisely those mutations." ### The lead authors of the study are Austin Dulak, PhD, and Petar Stojanov of Dana-Farber and the Broad Institute. Co-authors are: Shouyong Peng, PhD, Cameron Fox and Yu Imamura, MD, PhD, of Dana-Farber; Michael Lawrence, PhD, Chip Stewart, Erica Shefler, Aaron McKenna, Scott Carter, PhD, Kristian Cibulskis, Andrey Sivachenko, Gordon Saksena, Douglas Voet, Alex Ramos, PhD, Daniel Auclair, PhD, Kristin Thompson, PhD, Carrie Sougnez, Robert Onofrio, Stacey Gabriel, PhD, and Candace Guiducci, of the Broad Institute; Steven Schumacher, of Dana-Farber and the Broad; Rameen Beroukhim, MD, PhD, of Dana-Farber, the Broad Institute, and Brigham and Women's Hospital; Shuji Ogino, MD, PhD, of Dana-Farber, Brigham and Women's, and the Harvard School of Public Health; Todd Golub, MD, of Dana-Farber, the Broad Institute, and the Howard Hughes Medical Institute; Santhoshi Bandla, PhD, Tony Godfrey, PhD, and Zhongren Zhou, PhD, of the University of Rochester; Lin Lin, MD, PhD, Jules Lin, MD, Rishindra Reddy, MD, David Beer, PhD, and Andrew Chang, MD, of the University of Michigan; James Luketich, MD, Rodney Landrenau, MD, and Arjun Pennathur, MD, of the University of Pittsburgh Medical Center; and Eric Lander, DPhil, of the Broad Institute, and MIT. The work was supported in part by grants from the U.S. National Human Genome Research Institute (U54 HG003067), the National Cancer Institute (K08 CA134931), the DeGregorio Family Foundation, the Karin Grunebaum Cancer Research Foundation, Target Cancer, and Connecticut Conquers Cancer. About Dana-Farber Cancer Institute Dana-Farber Cancer Institute is a principal teaching affiliate of the Harvard Medical School and is among the leading cancer research and care centers in the United States. It is a founding member of the Dana-Farber/Harvard Cancer Center (DF/HCC), designated a comprehensive cancer center by the National Cancer Institute. It provides adult care with Brigham and Women's Hospital as Dana-Farber/Brigham and Women's Cancer Center, and it provides pediatric care with Boston Children's Hospital as Dana-Farber/Children's Hospital Cancer Center. Dana-Farber is the top-ranked cancer center in New England, according to U.S. News & World Report, and one of the largest recipients among independent hospitals of National Cancer Institute and National Institutes of Health grant funding. Follow Dana-Farber on Twitter or Facebook.

About the Broad Institute of MIT and Harvard The Eli and Edythe L. Broad Institute of MIT and Harvard was founded in 2003 to empower this generation of creative scientists to transform medicine with new genome-based knowledge. The Broad Institute seeks to describe all the molecular components of life and their connections; discover the molecular basis of major human diseases; develop effective new approaches to diagnostics and therapeutics; and disseminate discoveries, tools, methods and data openly to the entire scientific community.

Founded by MIT, Harvard and its affiliated hospitals, and the visionary Los Angeles philanthropists Eli and Edythe L. Broad, the Broad Institute includes faculty, professional staff and students from throughout the MIT and Harvard biomedical research communities and beyond, with collaborations spanning over a hundred private and public institutions in more than 40 countries worldwide. For further information about the Broad Institute, go to http://www.broadinstitute.org.

Contact: Anne Doerr
Anne_doerr@dfci.harvard.edu Rob Levy
Robert_Levy@dfci.harvard.edu
(617) 632-4090


ELSE PRESS RELEASES FROM THIS DATE:

Amniotic fluid stem cells repair gut damage

2013-03-25
Stem cells taken from amniotic fluid were used to restore gut structure and function following intestinal damage in rodents, in new research published in the journal Gut. The findings pave the way for a new form of cell therapy to reverse serious damage from inflammation in the intestines of babies. The study, funded by Great Ormond Street Hospital Children's Charity, investigated a new way to treat necrotizing enterocolitis (NEC), where severe inflammation destroys tissues in the gut. NEC is the most common gastrointestinal surgical emergency in newborn babies, with ...

UT MD Anderson scientists uncover the nuclear life of actin

2013-03-25
HOUSTON -- A key building block of life, actin is one of the most abundant and highly conserved proteins in eukaryotic cells. First discovered in muscle cells more than 70 years ago, actin has a well-established identity as a cytoplasmic protein that works by linking itself in chains to form filaments. Fibers formed by these actin polymers are crucial to muscle contraction. So it came as a surprise when scientists discovered actin in the nucleus. Labs have been working for the past few decades to figure out exactly what it's doing there. A new study published this ...

Sexually abused or neglected adolescent girls at risk of becoming moms while still teenagers

2013-03-25
Abused or neglected teenage girls become teen mothers at nearly five times the national rate of teen motherhood. A new Cincinnati Children's Hospital Medical Center study, published in the eFirst pages of the journal Pediatrics, shows that teen childbirth rates are more than 20 percent for abused and neglected teens. This compares to the national teen childbirth rate of approximately 4 percent. The finding holds true even after taking into account such factors as race, family income and whether the family was a one- or two-parent household. "Teen victims of sexual ...

Genetic alterations linked with bladder cancer risk, recurrence, progression, and patient survival

2013-03-25
A new analysis has found that genetic alterations in a particular cellular pathway are linked with bladder cancer risk, recurrence, disease progression, and patient survival. Published early online in CANCER, a peer- reviewed journal of the American Cancer Society, the findings could help improve bladder cancer screening and treatment. Alterations in the regulators of G-protein signaling (RGS) pathway, which is important for various cellular processes, have been implicated in several cancers. Eugene Lee, MD, of the MD Anderson Cancer Center in Houston, and his colleagues ...

New urgency in battle against 'bound legs' disease

2013-03-25
The harm done by konzo – a disease overshadowed by the war and drought it tends to accompany – goes beyond its devastating physical effects to impair children's memory, problem solving and other cognitive functions. Even children without physical symptoms of konzo appear to lose cognitive ability when exposed to the toxin that causes the disease, researchers report in the journal Pediatrics. "That's what's especially alarming," said lead author Michael Boivin, a Michigan State University associate professor of psychiatry and of neurology and ophthalmology. "We found ...

Global scientific experts convene in Cape Town to report on progress toward tuberculosis vaccines

2013-03-25
Contact: Jamie Rosen jrosen@aeras.org 27-766-593-409 Aeras Contact: Alison September a.september@uct.ac.za SATVI Contact: Erna Balk Erna.Balk@tbvi.eu 31-320-277-552 TuBerculosis Vaccine Initiative Global scientific experts convene in Cape Town to report on progress toward tuberculosis vaccines South Africa recognized as innovator in worldwide effort to address disease, as global concerns rise over drug-resistant strains CAPE TOWN – 25 March 2013 – At a time of growing global concern about the rising level of drug-resistant strains of tuberculosis ...

Wyndham Jade to Unveil New Mobile-Friendly Housing Platform

2013-03-25
During the Association Day 2013 conference and trade show, Wyndham Jade will introduce its mobile-friendly housing platform - RoomLogicTM - which helps associations maximize room blocks and enhance the hotel booking process for their customers. Hosted by Dallas Fort Worth Association Executives, Association Day will take place March 25 from 8 a.m. to 5 p.m. at the Fort Worth Convention Center. Wyndham Jade will provide demonstrations of RoomLogicTM in booth #34 from 11:15 a.m. to 1:30 p.m. RoomLogicTM websites automatically redraw themselves, creating a streamlined, ...

Adagold to Exhibit at the 2013 CQ Expo, 13-14 March, Rockhampton Show Grounds, Central Queensland

2013-03-25
Adagold Aviation will for the first time be exhibiting at the 2013 CQ Expo, held at Rockhampton Show Grounds on the 13-14 March. Now in its second year, the CQ Expo (Central Queensland Transport, Trades and Mining Expo) is fast becoming one of Central Queensland's key resources industry events. Adagold's Cairns-based Business Development Manager, Tracey Fisher will be onsite throughout the Expo to discuss your potential aircraft charter requirements, "This is the first time an aircraft charter solutions company such as Adagold has exhibited at the Expo, and we are ...

Raleigh Plastic Surgery Center's Dr. Jeremy Pyle Receives American Board of Plastic Surgery Certification

2013-03-25
Raleigh Plastic Surgery Center, a leading provider of aesthetic and reconstructive excellence for over 35 years, is pleased to announce that Dr. Jeremy Pyle has successfully completed certification by the American Board of Plastic Surgery (ABPS). Dr. Pyle received his certification after completing six years of residency training in an accredited plastic surgery program, passing comprehensive written and oral exams, and undergoing a review by the Board of all the procedures performed during the first part of his career. Dr. Pyle has been a surgeon with Raleigh Plastic ...

Air Guitar UK - Who Will be Crowned the UK's Greatest Air Guitarist?

2013-03-25
Gurning, bog snorkelling, and even worm charming, the UK has its fair share of weird and wonderful competitions, and the annual Air Guitar UK Championships are no exception. Leave your musical pretensions at the door and prepare to be wowed by a crowd of oddball competitors from across the country who've raised this often frowned-upon dance floor compulsion in to an art form in its own right. Overseeing proceedings will be a line-up of top comedians, performers and musicians, including cult fantasy author Robert Rankin, and along with the glamour and glory, the winner ...

LAST 30 PRESS RELEASES:

New register opens to crown Champion Trees across the U.S.

A unified approach to health data exchange

New superconductor with hallmark of unconventional superconductivity discovered

Global HIV study finds that cardiovascular risk models underestimate for key populations

New study offers insights into how populations conform or go against the crowd

Development of a high-performance AI device utilizing ion-controlled spin wave interference in magnetic materials

WashU researchers map individual brain dynamics

Technology for oxidizing atmospheric methane won’t help the climate

US Department of Energy announces Early Career Research Program for FY 2025

PECASE winners: 3 UVA engineering professors receive presidential early career awards

‘Turn on the lights’: DAVD display helps navy divers navigate undersea conditions

MSU researcher’s breakthrough model sheds light on solar storms and space weather

Nebraska psychology professor recognized with Presidential Early Career Award

New data shows how ‘rage giving’ boosted immigrant-serving nonprofits during the first Trump Administration

Unique characteristics of a rare liver cancer identified as clinical trial of new treatment begins

From lab to field: CABBI pipeline delivers oil-rich sorghum

Stem cell therapy jumpstarts brain recovery after stroke

Polymer editing can upcycle waste into higher-performance plastics

Research on past hurricanes aims to reduce future risk

UT Health San Antonio, UTSA researchers receive prestigious 2025 Hill Prizes for medicine and technology

Panorama of our nearest galactic neighbor unveils hundreds of millions of stars

A chain reaction: HIV vaccines can lead to antibodies against antibodies

Bacteria in polymers form cables that grow into living gels

Rotavirus protein NSP4 manipulates gastrointestinal disease severity

‘Ding-dong:’ A study finds specific neurons with an immune doorbell

A major advance in biology combines DNA and RNA and could revolutionize cancer treatments

Neutrophil elastase as a predictor of delivery in pregnant women with preterm labor

NIH to lead implementation of National Plan to End Parkinson’s Act

Growth of private equity and hospital consolidation in primary care and price implications

Online advertising of compounded glucagon-like peptide-1 receptor agonists

[Press-News.org] Study finds molecular 'signature' for rapidly increasing form of esophageal cancer