Oncologic surveillance for subjects with biallelic mismatch repair gene mutations: 10 year follow‐up of a kindred
Open Access
- 16 December 2011
- journal article
- research article
- Published by Wiley in Pediatric Blood & Cancer
- Vol. 59 (4), 652-656
- https://doi.org/10.1002/pbc.24019
Abstract
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.This publication has 17 references indexed in Scilit:
- Cancer Risks Associated With Germline Mutations in MLH1, MSH2, and MSH6 Genes in Lynch SyndromeJAMA, 2011
- Biochemical and imaging surveillance in germline TP53 mutation carriers with Li-Fraumeni syndrome: a prospective observational studyThe Lancet Oncology, 2011
- The Gastrointestinal Phenotype of Germline Biallelic Mismatch Repair Gene MutationsThe American Journal of Gastroenterology, 2010
- Hereditary and Familial Colon CancerGastroenterology, 2010
- Constitutional mismatch repair-deficiency syndrome: have we so far seen only the tip of an iceberg?Human Genetics, 2008
- Café‐au‐lait macules and pediatric malignancy caused by biallelic mutations in the DNA mismatch repair (MMR) gene PMS2Pediatric Blood & Cancer, 2008
- Constitutive deficiency in DNA mismatch repairClinical Genetics, 2007
- Recommendations for the Care of Individuals With an Inherited Predisposition to Lynch SyndromeJAMA, 2006
- Syndrome of Early Onset Colon Cancers, Hematologic Malignancies & Features of Neurofibromatosis in HNPCC Families with Homozygous Mismatch Repair Gene MutationsFamilial Cancer, 2005
- Controlled 15-year trial on screening for colorectal cancer in families with hereditary nonpolyposis colorectal cancerGastroenterology, 2000