Germline rearrangements in families with strong family history of glioma and malignant melanoma, colon, and breast cancer

Neuro Oncol. 2014 Oct;16(10):1333-40. doi: 10.1093/neuonc/nou052. Epub 2014 Apr 9.

Abstract

Background: Although familial susceptibility to glioma is known, the genetic basis for this susceptibility remains unidentified in the majority of glioma-specific families. An alternative approach to identifying such genes is to examine cancer pedigrees, which include glioma as one of several cancer phenotypes, to determine whether common chromosomal modifications might account for the familial aggregation of glioma and other cancers.

Methods: Germline rearrangements in 146 glioma families (from the Gliogene Consortium; http://www.gliogene.org/) were examined using multiplex ligation-dependent probe amplification. These families all had at least 2 verified glioma cases and a third reported or verified glioma case in the same family or 2 glioma cases in the family with at least one family member affected with melanoma, colon, or breast cancer.The genomic areas covering TP53, CDKN2A, MLH1, and MSH2 were selected because these genes have been previously reported to be associated with cancer pedigrees known to include glioma.

Results: We detected a single structural rearrangement, a deletion of exons 1-6 in MSH2, in the proband of one family with 3 cases with glioma and one relative with colon cancer.

Conclusions: Large deletions and duplications are rare events in familial glioma cases, even in families with a strong family history of cancers that may be involved in known cancer syndromes.

Keywords: CDKN2A/B; MLH1; MSH2; TP53; family history; glioma.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adult
  • Brain Neoplasms / genetics*
  • Breast Neoplasms / genetics*
  • Checkpoint Kinase 2 / genetics
  • Child, Preschool
  • Colonic Neoplasms / genetics*
  • Cyclin-Dependent Kinase Inhibitor p15 / genetics
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics
  • Female
  • Genetic Predisposition to Disease
  • Germ-Line Mutation*
  • Glioma / genetics*
  • Humans
  • Male
  • Melanoma / genetics*
  • Middle Aged
  • MutL Protein Homolog 1
  • MutS Homolog 2 Protein / genetics*
  • Nuclear Proteins / genetics
  • Pedigree
  • Tumor Suppressor Protein p53 / genetics
  • Young Adult

Substances

  • Adaptor Proteins, Signal Transducing
  • CDKN2B protein, human
  • Cyclin-Dependent Kinase Inhibitor p15
  • Cyclin-Dependent Kinase Inhibitor p16
  • MLH1 protein, human
  • Nuclear Proteins
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Checkpoint Kinase 2
  • CHEK2 protein, human
  • MSH2 protein, human
  • MutL Protein Homolog 1
  • MutS Homolog 2 Protein