(Press-News.org) Chromosomal deletions in DNA often involve just one of two gene copies inherited from either parent. But scientists haven't known how a deletion in one gene from one parent, called a "hemizygous" deletion, can contribute to cancer.
A research team led by Stephen Elledge, a professor in the Department of Genetics at Harvard Medical School, and his post-doctoral fellow Nicole Solimini, has now provided an answer. The most common hemizygous deletions in cancer, their research shows, involve a variety of tumor suppressing genes called STOP genes (suppressors of tumorigenesis and proliferation) that scatter randomly throughout the genome, but that sometimes cluster in the same place on a chromosome. And these clusters, said Elledge, who is also a professor of medicine at Brigham and Women's Hospital, tend to be deleted as a group. "Eliminating the cluster gives a bigger bang for the deletion buck," he said.
This finding is especially interesting in light of the two-hit model of cancer formation, which holds that both copies of a recessive gene need to be inactivated to trigger a biological effect. Thus the loss of a single tumor suppressor copy should have little or no influence on tumor cell proliferation because the remaining copy located on the other chromosome is there to pick up the slack.
Elledge's research points to a different hypothesis, namely that STOP genes in a hemizygous deletion aren't recessive but are instead haploinsufficient, meaning that they depend on two copies to function normally. "If a tumor suppressor is haploinsufficient, then a single gene copy lacks the potency needed to fully restrain tumorigenesis," Elledge explained, who is also a Howard Hughes Medical Institute Investigator. "So by removing clusters of haploinsufficient genes all at once, the cancer cell immediately propels its growth forward without having to wait for the other copies to also be lost."
Angelika Amon, a professor of biology at the Massachusetts of Technology, said she's surprised by the findings. "We've known from a lot of human syndromes that haploinsufficiency is widespread in the development of complex multicellular organisms," she said. "But these data show it's also critical for individual cells and cell proliferation."
The results also offer a different take on the two-hit model in carcinogenesis, Amon said. Being remarkably unstable, cancer cells can delete gene copies at every turn of the corner. If the loss of a single tumor suppressor copy provides no survival advantage for the tumor, then the tumor has no incentive to retain the cell with that deletion. But if the loss of that copy boosts proliferation, then the probability of a second hit later is greatly increased. "So haploinsufficiency is a way for the cancer cell to dramatically accelerate the acquisition of growth beneficial mutations," Amon said.
In other words, all it takes is a 50 percent reduction in gene activity for a cancer cell to grow. "That tells us it's a lot easier to get cancer than we might have hoped," Amon said.
According to Elledge, the number of hemizygotic deletions averages roughly six per tumor, with some tumors—breast and pancreatic, for instance—averaging up to ten. Each deletion involves 25 to 40 genes, many of them STOP genes, but also a few GO genes (growth enhancers and oncogenes) that enhance proliferation. That the STOP genes substantially outnumber their GO counterparts is important, Elledge explained, because it means cancer cells can tilt scales toward proliferation without also compromising it at the same time.
"The data reveal a lot of haploinsufficient players that have small effects individually, but large effects in combination," Elledge said. "Unfortunately, it's not easy to see how to take advantage of that chemotherapeutically."
What's important about the results, he emphasized, is that they open up new views on how tumors evolve. Moreso, they underscore the importance of proliferation as a fundamental feature of tumor growth, he added.
The challenge now, Elledge said, will be to find out which of the genes in a recurring deletion are haploinsufficient. "At the moment, we estimate roughly 25 percent," he said. "So these findings could also have important ramifications for other human diseases in addition to cancer."
###This work was supported by grants from the NCI/NHGRI funded Cancer Genome Atlas (TCGA) project, from the NIH (U54CA143798) to R.B. and by grants from the NIH, SU2C, and DOD.
Written by Charles Schmidt
Citation:
Science, May 24, 2012
"Recurrent Hemizygous Deletions in Cancers May Optimize Proliferative Potential," by Solimini et al.
Harvard Medical School has more than 7,500 full-time faculty working in 11 academic departments located at the School's Boston campus or in one of 47 hospital-based clinical departments at 17 Harvard-affiliated teaching hospitals and research institutes. Those affiliates include Beth Israel Deaconess Medical Center, Brigham and Women's Hospital, Cambridge Health Alliance, Children's Hospital Boston, Dana-Farber Cancer Institute, Forsyth Institute, Harvard Pilgrim Health Care, Hebrew SeniorLife, Joslin Diabetes Center, Judge Baker Children's Center, Massachusetts Eye and Ear Infirmary, Massachusetts General Hospital, McLean Hospital, Mount Auburn Hospital, Schepens Eye Research Institute, Spaulding Rehabilitation Hospital, and VA Boston Healthcare System.
New study suggests #cancer cells may grow more easily than researchers have hoped. Simpler mutations the culprit. http://hvrd.me/JBSPcx
Cancer may require simpler genetic mutations than previously thought
Findings suggest cancer cells may grow more easily than researchers and clinicians have hoped
2012-05-28
ELSE PRESS RELEASES FROM THIS DATE:
UMass Amherst wildlife researcher photographs rare Sumatran rabbit
2012-05-28
AMHERST, Mass. – Using camera traps, wildlife researchers including doctoral candidate Jennifer McCarthy and environmental conservation professor Todd Fuller of the University of Massachusetts Amherst recently captured photographs of one of the rarest animals on earth, the Sumatran striped rabbit. They say it may now be found only in two remote national parks on the Indonesian island.
Their pictures and other observations are reported in the current issue of Oryx, The International Journal of Conservation. The rare rabbit was first photographed in Kerinci Seblat National ...
Early physical therapist treatment associated with reduced risk of healthcare utilization and reduced overall healthcare costs
2012-05-28
ALEXANDRIA, VA, May 25, 2012 – A new study published in Spine shows that early treatment by a physical therapist for low back pain (LBP), as compared to delayed treatment, was associated with reduced risk of subsequent healthcare utilization and lower overall healthcare costs.
Using a national database of employer-sponsored health plans, researchers examined a sample of 32,070 patients who were newly consulting a primary care physician for low back pain. Patients were identified and categorized based on their use of physical therapist services within 90 days of the ...
Ferret.com Believes in The Ferret Squad Movie!
2012-05-28
Ferret.com (www.ferret.com), an online retailer based out of Pennsylvania, that sells a vast variety of ferret products, is the most recent corporation to make a donation to assist in the making of the independent feature film, The Ferret Squad. Ferret.com is a subsidiary of TABcom LLC. TABcom LLC, founded in 1969, is the parent company to a wide variety of pet-related websites, including Dog.com, Bird.com, Horse.com, Ferret.com, Fish.com and StateLineTack.com. All sites provide a broad range of competitively priced pet supplies, as well as community forums and partnerships ...
Math predicts size of clot-forming cells
2012-05-28
VIDEO:
This animation from a computer model shows how forces from proteins in the larger pre-platelet form the barbell-shaped pro-platelet. Proplatelets form platelets of the correct size and shape....
Click here for more information.
UC Davis mathematicians have helped biologists figure out why platelets, the cells that form blood clots, are the size and shape that they are. Because platelets are important both for healing wounds and in strokes and other conditions, a better ...
NASA sees Hurricane Bud threaten western Mexico's coast
2012-05-28
NASA satellites are providing rainfall, temperature, pressure, visible and infrared data to forecasters as Hurricane Bud is expected to make a quick landfall in western Mexico this weekend before turning back to sea. NASA's TRMM and Aqua satellites have been flying over Bud as it nears the Mexican coast.
NASA's Tropical Rainfall Measuring Mission (TRMM) satellite passed above Hurricane Bud early this morning, May 25 at 0429 UTC (12:49 a.m. EDT/U.S.). A large area of moderate to heavy rainfall with rates of over 30mm/hr (~1.2 inches) was revealed in Bud by TRMM's Microwave ...
National Mail Order Promotes American Ingenuity with the 'Made in America Hot Product Contest'
2012-05-28
According to a recent article from ABC News, President Obama is indicating the recovery of American manufacturing as a leap toward an "economy built to last".(1). In conjunction with this and their 40th Anniversary in business, the National Mail Order Association (NMOA) commences their national Made in America Hot Product Contest beginning on June 1, 2012. NMOA is looking for as many American manufacturers as possible to have the chance to enter their product for the world to see. NMOA's Made in America Hot Product Contest has one main goal: helping the thousands ...
Aegis Power Systems Announces the Availability of its VME550 DC-DC Power Converter.
2012-05-28
AEGIS Power Systems Inc., a custom power supply designer and manufacturer has released and made immediately available its latest VME Power Converter Card. The VME550 Series of ruggedized industrial power converters are designed for mil-cots, defense, aerospace, telecom, and industrial applications. This newest VME power converter card family is available in a single slot 6U x 4hp x 160mm conduction cooled card, VME550; or in a dual slot 6U x 8hp x 160mm air cooled card with heat-sink, VME550A. The VME550 series operates with a nominal input of 28VDC (22VDC - 33VDC) and ...
Boast Capital Partners with Plug and Play Tech Center To Launch Startup Camp Canada
2012-05-28
Boast Capital is proud to announce a partnership with Plug and Play Tech Center in Silicon Valley to launch Startup Camp Canada, an initiative to support and grow the Information and Communications Technology (ICT) sector in Alberta.
The hybrid accelerator program will provide startups with acceleration time in both Canada and Silicon Valley with access to over 180 Silicon Valley venture capital (VC) firms and angel investors such as Accel Partners and Sand Hill Angels, world-class entrepreneurs from companies such as YouTube and Skype, and a community of leading universities ...
Typhoon Sanvu affecting Iwo To, then expected to fade over weekend
2012-05-28
VIDEO:
This animation of Typhoon Sanvu was created from 3-D images of TRMM satellite data during the week of May 21, 2012, as the storm moved through the western North Pacific...
Click here for more information.
Infrared and visible imagery from NASA's Aqua satellite taken on May 25, 2012, showed an impressive Typhoon Sanvu already affecting the islands of Iwo To and Chichi Jima, Japan. The typhoon is expected to run into cooler waters and become extra-tropical over the ...
Famous Historic Beaumont Hotel Celebrates 125 years
2012-05-28
Beaumont Hotel & Spa commemorates its 125th Anniversary with a new restaurant and lounge inside the hotel called Ore House Bar & Grill and Luella's Lounge. The festivities will continue from 11am to 4pm June 2, 2012. During the event, guests will enjoy an unusual Victorian-Era Fashion Show, live music, a ribbon cutting for the restaurant, free hotel tours and free massages in the spa & A Tribute to Fallen Miners will honor the miners of old Ouray. Prizes include a priceless & rare bottle of wine, spa services, dinners, a stay at the hotel, and so much more. ...
LAST 30 PRESS RELEASES:
Plant doctor: An AI system that watches over urban trees without touching a leaf
Study tracks chromium chemistry in irradiated molten salts
Scientists: the beautiful game is a silver bullet for global health
Being physically active, even just a couple of days a week, may be key to better health
High-fat diet promote breast cancer metastasis in animal models
A router for photons
Nurses and AI collaborate to save lives, reduce hospital stays
Multi-resistance in bacteria predicted by AI model
Tinker Tots: A citizen science project to explore ethical dilemmas in embryo selection
Sensing sickness
Cost to build multifamily housing in California more than twice as high as in Texas
Program takes aim at drinking, unsafe sex, and sexual assault on college campuses
Inability to pay for healthcare reaches record high in U.S.
Science ‘storytelling’ urgently needed amid climate and biodiversity crisis
KAIST Develops Retinal Therapy to Restore Lost Vision
Adipocyte-hepatocyte signaling mechanism uncovered in endoplasmic reticulum stress response
Mammals were adapting from life in the trees to living on the ground before dinosaur-killing asteroid
Low LDL cholesterol levels linked to reduced risk of dementia
Thickening of the eye’s retina associated with greater risk and severity of postoperative delirium in older patients
Almost one in ten people surveyed report having been harmed by the NHS in the last three years
Enhancing light control with complex frequency excitations
New research finds novel drug target for acute myeloid leukemia, bringing hope for cancer patients
New insight into factors associated with a common disease among dogs and humans
Illuminating single atoms for sustainable propylene production
New study finds Rocky Mountain snow contamination
Study examines lactation in critically ill patients
UVA Engineering Dean Jennifer West earns AIMBE’s 2025 Pierre Galletti Award
Doubling down on metasurfaces
New Cedars-Sinai study shows how specialized diet can improve gut disorders
Making moves and hitting the breaks: Owl journeys surprise researchers in western Montana
[Press-News.org] Cancer may require simpler genetic mutations than previously thoughtFindings suggest cancer cells may grow more easily than researchers and clinicians have hoped