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CDKN2A founder mutation in pancreatic ductal adenocarcinoma patients without cutaneous features of Familial Atypical Multiple Mole Melanoma (FAMMM) syndrome. | LitMetric

AI Article Synopsis

Article Abstract

Background: Approximately 5% to 10% of pancreatic ductal adenocarcinoma (PDAC) has a hereditary basis. In most of these defined hereditary cancer syndromes, PDAC is not the predominant cancer type. Traditional criteria for publicly funded genetic testing typically require the presence of a set combination of the predominant syndrome-associated cancer types in the family history.We report the identification of a pathogenic variant in a PDAC-prone family without the cutaneous features of multiple moles or melanoma that are characteristic of the Familial Atypical Multiple Mole Melanoma (FAMMM) Syndrome identified in a universal testing algorithm for inherited mutations in pancreatic cancer patients.

Case Presentation: We present the case of two brothers of English ancestry diagnosed with PDAC within the same 12 month period, at the respective ages of 63 and 64 years of age. Neither brother reported a personal history of multiple moles or melanoma. Family history was positive for two second-degree relatives diagnosed with PDAC but was negative for other cancers or multiple moles in first- and second-degree relatives. Due to the absence of melanoma, this family did not meet provincial criteria for publicly funded genetic testing. Clinical genetic testing offered through a research grant identified a pathogenic variant in the gene c.377 T > A (p.Val126Asp). This variant is a North American founder mutation believed to pre-date colonization.

Conclusions: This case reminds clinicians to consider the possibility of a germline mutation in families with a high prevalence of PDAC, even in the absence of moles or melanoma. This case supports recent guidelines published by the American College of Medical Genetics and Genomics (ACMG) that genetics referrals are indicated in families with three or more cases of PDAC regardless of other cancer types in the family. A multi-gene panel approach is of particular benefit in diagnosing inherited cancer susceptibility in PDAC-only families.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5842519PMC
http://dx.doi.org/10.1186/s13053-018-0088-yDOI Listing

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