Oncologic surveillance for subjects with biallelic mismatch repair gene mutations: 10 year follow-up of a kindred

Pediatr Blood Cancer. 2012 Oct;59(4):652-6. doi: 10.1002/pbc.24019. Epub 2011 Dec 16.


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.

MeSH terms

  • Adolescent
  • Adult
  • Alleles
  • Child
  • Colorectal Neoplasms, Hereditary Nonpolyposis / diagnosis
  • Colorectal Neoplasms, Hereditary Nonpolyposis / genetics*
  • Colorectal Neoplasms, Hereditary Nonpolyposis / surgery
  • DNA Mismatch Repair / genetics*
  • Female
  • Follow-Up Studies
  • Genetic Testing
  • Germ-Line Mutation*
  • Humans
  • Male
  • Neoplastic Syndromes, Hereditary / diagnosis
  • Neoplastic Syndromes, Hereditary / genetics*
  • Neoplastic Syndromes, Hereditary / surgery
  • Pedigree