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

M. Alonso, R. Hamelin, Mimi Kim, K. Porwancher, T. Sung, P. Parhar, D. C. Miller, E. W. Newcomb

Research output: Contribution to journalArticle

60 Citations (Scopus)

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

Fingerprint

Central Nervous System Neoplasms
Microsatellite Instability
Pediatrics
DNA Mismatch Repair
p53 Genes
Astrocytoma
Adenine
Microsatellite Repeats
Ganglioglioma
Neoplasms
Mutation
National Cancer Institute (U.S.)
Incidence
Glioblastoma
Endometrial Neoplasms
Colonic Neoplasms
Stomach Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Alonso, M., Hamelin, R., Kim, M., Porwancher, K., Sung, T., Parhar, P., ... 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.

Microsatellite instability occurs in distinct subtypes of pediatric but not adult central nervous system tumors. / Alonso, M.; Hamelin, R.; Kim, Mimi; Porwancher, K.; Sung, T.; Parhar, P.; Miller, D. C.; Newcomb, E. W.

In: Cancer Research, Vol. 61, No. 5, 01.03.2001, p. 2124-2128.

Research output: Contribution to journalArticle

Alonso, M, Hamelin, R, Kim, M, Porwancher, K, Sung, T, Parhar, P, Miller, DC & Newcomb, EW 2001, 'Microsatellite instability occurs in distinct subtypes of pediatric but not adult central nervous system tumors', Cancer Research, vol. 61, no. 5, pp. 2124-2128.
Alonso M, Hamelin R, Kim M, Porwancher K, Sung T, Parhar P et al. Microsatellite instability occurs in distinct subtypes of pediatric but not adult central nervous system tumors. Cancer Research. 2001 Mar 1;61(5):2124-2128.
Alonso, M. ; Hamelin, R. ; Kim, Mimi ; Porwancher, K. ; Sung, T. ; Parhar, P. ; Miller, D. C. ; Newcomb, E. W. / Microsatellite instability occurs in distinct subtypes of pediatric but not adult central nervous system tumors. In: Cancer Research. 2001 ; Vol. 61, No. 5. pp. 2124-2128.
@article{a8d8aa4f837a49a19bf6ee2d7f9a0c16,
title = "Microsatellite instability occurs in distinct subtypes of pediatric but not adult central nervous system tumors",
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.",
author = "M. Alonso and R. Hamelin and Mimi Kim and K. Porwancher and T. Sung and P. Parhar and Miller, {D. C.} and Newcomb, {E. W.}",
year = "2001",
month = "3",
day = "1",
language = "English (US)",
volume = "61",
pages = "2124--2128",
journal = "Cancer Research",
issn = "0008-5472",
publisher = "American Association for Cancer Research Inc.",
number = "5",

}

TY - JOUR

T1 - Microsatellite instability occurs in distinct subtypes of pediatric but not adult central nervous system tumors

AU - Alonso, M.

AU - Hamelin, R.

AU - Kim, Mimi

AU - Porwancher, K.

AU - Sung, T.

AU - Parhar, P.

AU - Miller, D. C.

AU - Newcomb, E. W.

PY - 2001/3/1

Y1 - 2001/3/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0035266426&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035266426&partnerID=8YFLogxK

M3 - Article

C2 - 11280776

AN - SCOPUS:0035266426

VL - 61

SP - 2124

EP - 2128

JO - Cancer Research

JF - Cancer Research

SN - 0008-5472

IS - 5

ER -