Microsatellite instability occurs in distinct subtypes of pediatric but not adult central nervous system tumors

Michelle Alonso, Richard Hamelin, Mimi Kim, Kara Porwancher, Tammy Sung, Preeti Parhar, Douglas C. Miller, Elizabeth W. Newcomb

Research output: Contribution to journalArticle

61 Scopus citations

Abstract

Length alterations in microsatellite repeats, termed microsatellite instability (MSI), are found in 10-15% of sporadic colon, endometrial, and gastric cancers harboring defects in DNA mismatch repair (MMR) genes. We used the microsatellite markers Big Adenine Tract (BAT) 26 and BAT-25 from the reference panel of five markers recommended by the National Cancer Institute to evaluate the incidence of MSI in 206 central nervous system tumors. We screened 102 pediatric and 104 adult cases representing 165 astrocytic and 41 nonastrocytic tumors. The overall incidence of MSI was 8% (16 of 206). All 16 tumors with MSI were found in pediatric rather than adult patients. MSI was associated with two distinct subtypes of pediatric tumors occurring in 27% (12 of 45) of WHO grade III and grade IV astrocytomas and 24% (4 of 17) of gangliogliomas. We evaluated the difference in clinicopathological and genetic features among 45 high-grade pediatric astrocytomas by MSI status. The median survival for pediatric patients with MSI (n = 12) was 8 months compared with 15 months for those patients without MSI (n = 33; P = 0.18). The frequency of p53 gene mutations was 13% for pediatric patients with MSI (n = 8) compared with 47% for those patients without MSI (n = 19; P = 0.19). These results revealed a trend between MSI status and prognosis and MSI status and frequency of p53 gene mutations. Our data suggest that pediatric high-grade astrocytomas can be attributed to two different genetic pathways: a MMR-deficient pathway and a MMR-proficient pathway.

Original languageEnglish (US)
Pages (from-to)2124-2128
Number of pages5
JournalCancer Research
Volume61
Issue number5
StatePublished - Mar 1 2001
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Microsatellite instability occurs in distinct subtypes of pediatric but not adult central nervous system tumors'. Together they form a unique fingerprint.

  • Cite this

    Alonso, M., Hamelin, R., Kim, M., Porwancher, K., Sung, T., Parhar, P., Miller, D. C., & Newcomb, E. W. (2001). Microsatellite instability occurs in distinct subtypes of pediatric but not adult central nervous system tumors. Cancer Research, 61(5), 2124-2128.