JAMA Network | JAMA: The Journal of the American Medical Association | APC Gene Testing for Familial Adenomatosis Polyposis

JAMA Network | JAMA: The Journal of the American Medical Association | APC Gene Testing for Familial Adenomatosis Polyposis

APC Gene Testing for Familial Adenomatosis Polyposis

Hemant K. Roy, MD; Janardan D. Khandekar, MD

[+-] Author Affiliations

Author Affiliations: Department of Medicine, NorthShore University HealthSystem, Evanston Illinois (Drs Roy and Khandekar).

JAMA. 2012;308(5):514-515. doi:10.1001/jama.2012.9516

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Although genomics is destined to revolutionize clinical medicine, to date its beneficial effects have been somewhat muted. The promise and perils of genomics are emblemized by one of its flagship applications, namely the diagnosis of familial adenomatosis polyposis (FAP). FAP is an autosomal dominant syndrome characterized by numerous colonic adenomas which, without recognition and intervention, generally result in development of early-onset colorectal cancer, along with higher risks of several other malignancies (eg, duodenum, pancreas, thyroid, brain). Approximately 2 decades ago, it was discovered that germline mutations of the adenomatous polyposis coli (APC) tumor suppressor gene with concomitant overactivity in the Wingless-type mouse mammary tumor virus integration site (WNT) signaling cascade were responsible for most (approximately 80%-90%) FAP cases.^{1 - 2} More recently, a small subset of FAP cases were attributed to biallelic germline mutations of the base excision–repair gene mutY homologue (MUTYH)³ .