“Individuals with an inherited form of skin cancer often have a poor prognosis. The type of immunotherapy that was awarded this year’s Nobel Prize in Physiology or Medicine is, however, particularly effective in this patient group, research from Karolinska Institutet in Sweden shows. The study is published in the Journal of Medical Genetics.
“Congenital mutations of the CDKN2A gene are the strongest known risk factors for inherited skin cancer. Individuals with melanoma who carry mutations in this gene also have poor prognosis, according to previous research.”
The gist: Some people whose families have high rates of melanoma may also have an increased risk of developing lung, pancreatic, and breast cancer. Specifically, people whose families have a mutation in the CDKN2A gene are more prone to developing other types of cancer. Oncologists can perform molecular testing to see whether a person has a CDKN2A mutation.
“Researchers discovered an increased prevalence of lung, pancreatic and breast cancer in families prone to melanoma who also carry CDKN2A germline mutations.
“In a cross-sectional study, researchers analyzed the effect of CDKN2A in 702 Spanish patients at high risk of developing melanoma and associations with clinical and family history features.
“Patients with sporadic multiple primary melanoma had a CDKN2A mutation prevalence of 8.5%, and those with familial melanoma had a CDKN2A mutation prevalence of 14.1%.
“The researchers found that the number of cases in the family, the number of primary melanomas and the age of onset were each associated with the presence of CDKN2A mutation.”
“Monitoring patients at extreme risk with total-body photography (TBP) and sequential digital dermoscopy imaging (SDDI) assists with early diagnosis of primary melanoma, according to a study published online June 25 in JAMA Dermatology.
“Fergal J. Moloney, M.D., from the University of Sydney, and colleagues compared six-month full-body examination versus TBP in 311 patients (February 2006 to February 2011). Patients had either a history of invasive melanoma and dysplastic nevus syndrome, a history of invasive melanoma and at least three first-degree or second-degree relatives with prior melanoma, a history of at least two primary invasive melanomas, or a CDKN2A or CDK4 gene mutation.”
Nathanson KL, Martin AM, Wubbenhorst B, Greshock J, et al. Clinical Cancer Research. Jul 5, 2013.
“Dabrafenib is a selective inhibitor of V600-mutant BRAF kinase, which recently demonstrated improved progression free survival (PFS) as compared with dacarbazine, in metastatic melanoma patients. The current study examined potential genetic markers associated with response and PFS in the phase I study of dabrafenib.”
Konstantinidou G, Ramadori G ... Teruya-Feldstein J, Scaglioni PP, Cancer Discov, Mar 21, 2013
Non–small cell lung cancer (NSCLC) often expresses mutant KRAS together with tumor-associated mutations of the CDKN2A locus, which are associated with aggressive, therapy-resistant tumors. Suppression of RHOA or FAK induces cell death selectively in mutant KRAS;INK4A/ARF-deficient lung cancer cells. Furthermore, pharmacologic inhibition of FAK caused tumor regression specifically in the high-grade lung cancer that developed in mutant Kras;Cdkn2a-null mice.