Beyond PTEN: Alternate genes linked to breast, thyroid and kidney cancer predisposition

Aug 07, 2008

A new discovery may lead to more effective screening and treatment for patients with a difficult to recognize syndrome characterized by tumor-like growths and a high risk of developing specific cancers. The research, published by Cell Press in the August 7 issue of the American Journal of Human Genetics, is the first in over thirteen years to identify an alternate susceptibility gene for Cowden syndrome (CS) and related disorders.

Mutations of the common tumor suppressor PTEN are associated with most cases of CS, a poorly recognized, inherited cancer syndrome that causes benign and malignant breast, thyroid and uterine tumors. However, about 15% of CS patients do not exhibit PTEN mutations and the cause for the disorder in these patients is unknown. Further, many patients present with a poorly understood CS-like syndromes that do not meet the diagnostic guidelines for CS. "Other susceptibility genes for CS and CS-like phenotypes must exist," says lead study author Dr. Charis Eng, the Hardis Chair and Director of the Genomic Medicine Institute at the Cleveland Clinic.

Succinate dehydrogenase (SDH) is a mitochondrial enzyme that is responsible for energy production and is therefore vital to all organs and organisms. Mutations in both copies of the SDH genes cause a rare devastating brain and heart condition resulting in death in infancy and childhood. Surprisingly, mutations in one of the pair of genes for various forms of SDH (referred to as SDHx) have been linked to a group of rare tumors called paragangliomas and pheochromocytomas. Dr. Eng noticed, however, that 1-5% of individuals with these rare tumors also had thyroid cancers similar to those observed in CS and CS-like patients. "We hypothesized that SDHx might represent susceptibility genes, other than PTEN, for CS/CS-like syndromes," explains Dr. Eng.

Dr. Eng and colleagues screened samples from CS/CS-like individuals that did not possess PTEN mutations for mitochondrial dysfunction. They identified a subset of patients with CS or CS-like syndrome that had various SDH mutations that were unrelated to PTEN mutations. Compared with PTEN mutation positive CS/CS-like individuals, those with SDH mutations exhibited a consistently increased risk for breast, thyroid and kidney cancers. Interestingly, in the absence of PTEN alteration, CS/CS-like-related SDH mutations exhibited perturbations of cellular signaling pathways similar to those seen in PTEN dysfunction.

"Our data have important implications for both patient care and genetic counseling. I would like to see others independently repeat our observations. Nonetheless, clinicians should consider SDH testing for PTEN mutation-negative CS/CS-like individuals, especially if these individuals have a strong personal history and/or family history of breast, thyroid or kidney cancer. In fact, patients with SDHx mutation should be more rigorously screened for these cancers compared to those with PTEN mutations," concludes Dr. Eng.

Source: Cell Press

Explore further: Science of romantic relationships includes gene factor

add to favorites email to friend print save as pdf

Related Stories

NASA issues 'remastered' view of Jupiter's moon Europa

7 hours ago

(Phys.org) —Scientists have produced a new version of what is perhaps NASA's best view of Jupiter's ice-covered moon, Europa. The mosaic of color images was obtained in the late 1990s by NASA's Galileo ...

Dish restores Turner channels to lineup

8 hours ago

Turner Broadcasting channels such as Cartoon Network and CNN are back on the Dish network after being dropped from the satellite TV provider's lineup during contract talks.

LiquidPiston unveils quiet X Mini engine prototype

13 hours ago

LiquidPiston has a new X Mini engine which is a small 70 cubic centimeter gasoline powered "prototype. This is a quiet, four-stroke engine with near-zero vibration. The company said it can bring improvements ...

Recommended for you

Science of romantic relationships includes gene factor

14 hours ago

(Medical Xpress)—Adolescents worry about passing tests, winning games, lost phones, fractured bones—and whether or not they will ever really fall in love. Three Chinese researchers have focused on that ...

Stress reaction may be in your dad's DNA, study finds

Nov 21, 2014

Stress in this generation could mean resilience in the next, a new study suggests. Male mice subjected to unpredictable stressors produced offspring that showed more flexible coping strategies when under ...

More genetic clues found in a severe food allergy

Nov 21, 2014

Scientists have identified four new genes associated with the severe food allergy eosinophilic esophagitis (EoE). Because the genes appear to have roles in other allergic diseases and in inflammation, the ...

Brain-dwelling worm in UK man's head sequenced

Nov 20, 2014

For the first time, the genome of a rarely seen tapeworm has been sequenced. The genetic information of this invasive parasite, which lived for four years in a UK resident's brain, offers new opportunities ...

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.