Genetic analyses for predictors of radiation response in glioblastoma

Helen A. Shih, Rebecca Betensky, Molly V. Dorfman, David N. Louis, Jay S. Loeffler, Tracy T. Batchelor

Research output: Contribution to journalArticle

Abstract

Purpose: Radiotherapy (RT) for patients with glioblastoma improves survival and is recommended for nearly all patients with this diagnosis. However, the response to RT is variable in this patient population. Prior studies have suggested that underlying genetic alterations in the tumor may account for some of this treatment-related heterogeneity. It has been previously reported that epidermal growth factor receptor (EGFR) gene amplification and TP53 mutation correlate with the response to RT in patients with glioblastoma. Methods and Materials: We sought to identify molecular markers that could predict the response to RT, progression-free survival after RT, and overall survival among 75 glioblastoma patients treated with RT at a single institution. Genetic analyses assessed EGFR amplification, TP53 mutations, CDKN2A/p16 deletion, and losses of chromosomes 1p, 10q, and 19q. Results: Unlike previous reports, no association of EGFR amplification with response to RT, progression-free survival, or overall survival was found. Moreover, no association was found between these endpoints and the other genetic alterations assayed (TP53 mutation, CDKN2A/p16 deletion, loss of heterozygosity 1p, loss of heterozygosity 10q, and loss of heterozygosity 19q). However, in accordance with recent observations that the prognostic effects of genetic alterations in glioblastoma may depend on patient age, we observed age-dependent prognostic effects of TP53 and CDKN2A/p16 alterations in our patient population. For patients <57 years old, those harboring TP53 mutations had a decreased overall survival compared with patients without TP53 mutations. Similarly, deletion of CDKN2A/p16 in patients <57 years was associated with decreased progression-free survival after RT and a trend toward a shorter time to progression after RT compared with similar patients without the deletion. Conclusion: These data contrast with previous studies regarding the significant prognostic effect of EGFR with respect to RT response. Although our observations regarding the age-dependent prognostic effects of TP53 and CDKN2A/p16 are consistent with a prior report regarding these alterations, the present results should be considered preliminary, given the small sample size.

Original languageEnglish (US)
Pages (from-to)704-710
Number of pages7
JournalInternational Journal of Radiation Oncology Biology Physics
Volume63
Issue number3
DOIs
StatePublished - Nov 1 2005

Fingerprint

Glioblastoma
radiation therapy
Radiotherapy
Radiation
radiation
predictions
mutations
deletion
progressions
Loss of Heterozygosity
Mutation
Epidermal Growth Factor Receptor
Disease-Free Survival
Survival
erbB-1 Genes
Chromosome Deletion
Gene Amplification
chromosomes
genes
Sample Size

Keywords

  • Genetics
  • Glioblastoma
  • Predictors
  • Radiotherapy response

ASJC Scopus subject areas

  • Radiation
  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

Cite this

Genetic analyses for predictors of radiation response in glioblastoma. / Shih, Helen A.; Betensky, Rebecca; Dorfman, Molly V.; Louis, David N.; Loeffler, Jay S.; Batchelor, Tracy T.

In: International Journal of Radiation Oncology Biology Physics, Vol. 63, No. 3, 01.11.2005, p. 704-710.

Research output: Contribution to journalArticle

Shih, Helen A. ; Betensky, Rebecca ; Dorfman, Molly V. ; Louis, David N. ; Loeffler, Jay S. ; Batchelor, Tracy T. / Genetic analyses for predictors of radiation response in glioblastoma. In: International Journal of Radiation Oncology Biology Physics. 2005 ; Vol. 63, No. 3. pp. 704-710.
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