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Oncologic surveillance for subjects with biallelic mismatch repair gene mutations: 10 year follow‐up of a kindred
Author(s) -
Durno Carol A.,
Aronson Melyssa,
Tabori Uri,
Malkin David,
Gallinger Steven,
Chan Helen S. L.
Publication year - 2012
Publication title -
pediatric blood and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.116
H-Index - 105
eISSN - 1545-5017
pISSN - 1545-5009
DOI - 10.1002/pbc.24019
Subject(s) - medicine , asymptomatic , lynch syndrome , dna mismatch repair , genetic testing , colorectal cancer , familial adenomatous polyposis , cancer , germline mutation , gene mutation , oncology , mutation , gene , genetics , biology
Background Heterozygous germline mutations in DNA mismatch repair (MMR) genes cause Lynch syndrome. Biallelic MMR mutations cause a distinct syndrome characterized by brain tumors, lymphoid malignancies, and gastrointestinal cancers during childhood. These children usually succumb to multiple cancers before adulthood. We developed a surveillance protocol aiming at early detection for these individuals and report the 10‐year experience with a kindred. Methods On the basis of genetic testing and early age tumors, the kindred started a cancer surveillance protocol based on the crude estimates of cancer risks and available cancer screening: imaging, endoscopy, and hematologic tests. Results Over the 10‐year follow‐up period, the screening protocol detected 15 tumors. These included three high‐grade adenomatous colonic polyps and two colon cancers. In one child, MRI revealed an asymptomatic anaplastic astrocytoma which was treated by complete resection and radiation. All three cancers identified during surveillance were small and asymptomatic at diagnosis. The two sisters are currently 16 and 18 years of age with no evidence of malignant disease. Both parents have annual colonoscopies and the father at 43 years had two colonic adenomatous polyps. Conclusions We report on the long‐term outcome in patients with biallelic MMR mutations who benefited from prophylactic cancer surveillance. Genetic screening and subsequent surveillance led to earlier recognition of asymptomatic tumors at stages more amenable to resection and probable cure. Multicenter collaboration and implementation of surveillance guidelines is necessary to further determine genotype–phenotype correlations. Pediatr Blood Cancer 2012;59:652–656. © 2011 Wiley Periodicals, Inc.