Lymphoid gene expression as a predictor of risk of secondary brain tumors

Mathew J. Edick, Cheng Cheng, Wenjian Yang, Meyling Cheok, Mark R. Wilkinson, Deqing Pei, William E. Evans, Larry E. Kun, Ching Hon Pui, Mary V. Relling

Research output: Contribution to journalArticle

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Abstract

Gene expression profiles are tissue-specific but may also reflect germ-line-driven expression patterns across tissue types. Previously, using a targeted pharmacologic approach, we identified germ-line polymorphisms in a single gene (thiopurine methyltransferase) associated with the risk of irradiation- and chemotherapy-induced secondary brain tumors in children with acute lymphoblastic leukemia (ALL). To identify additional candidate genetic risk factors, in identically treated patients, we compared the gene expression profiles of diagnostic ALL blasts of those who did develop irradiation- associated brain tumors (n = 9) with the profiles from those who did not (n = 33). Weighted rank regression was used to identify 33 probe sets associated with the time-dependent development of brain tumors; k-means clustering (k = 2) identified 2 groups that differed significantly in cumulative incidence of brain tumors (P = 0.012). Permutation analysis was used to estimate the probability (P = 0.18) of obtaining 2 such clusters by chance. Linear discriminant analysis (time-independent categorization of outcome) was used to identify 70 probe sets whose expression differentiated between the 2 groups of patients. Permutation analyses (n = 1,000) was used to estimate the probability of selecting these probe sets by chance (P = 0.055). Five probe sets were in common between the time-independent and time-dependent methods. The distinguishing genes are involved in neural growth (FGFRI) and in nuclear trafficking (HNRPL, KPNBI). These data suggest that gene expression profiling from accessible tissues may identify targets involved in therapy-related malignancies in unrelated tissues.

Original languageEnglish (US)
Pages (from-to)107-116
Number of pages10
JournalGenes Chromosomes and Cancer
Volume42
Issue number2
DOIs
StatePublished - Feb 1 2005

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Brain Neoplasms
Gene Expression
thiopurine methyltransferase
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Transcriptome
Germ Cells
Gene Expression Profiling
Discriminant Analysis
Genes
Cluster Analysis
Drug Therapy
Incidence
Growth
Neoplasms
Therapeutics

ASJC Scopus subject areas

  • Genetics
  • Cancer Research

Cite this

Edick, M. J., Cheng, C., Yang, W., Cheok, M., Wilkinson, M. R., Pei, D., ... Relling, M. V. (2005). Lymphoid gene expression as a predictor of risk of secondary brain tumors. Genes Chromosomes and Cancer, 42(2), 107-116. https://doi.org/10.1002/gcc.20121

Lymphoid gene expression as a predictor of risk of secondary brain tumors. / Edick, Mathew J.; Cheng, Cheng; Yang, Wenjian; Cheok, Meyling; Wilkinson, Mark R.; Pei, Deqing; Evans, William E.; Kun, Larry E.; Pui, Ching Hon; Relling, Mary V.

In: Genes Chromosomes and Cancer, Vol. 42, No. 2, 01.02.2005, p. 107-116.

Research output: Contribution to journalArticle

Edick, MJ, Cheng, C, Yang, W, Cheok, M, Wilkinson, MR, Pei, D, Evans, WE, Kun, LE, Pui, CH & Relling, MV 2005, 'Lymphoid gene expression as a predictor of risk of secondary brain tumors', Genes Chromosomes and Cancer, vol. 42, no. 2, pp. 107-116. https://doi.org/10.1002/gcc.20121
Edick MJ, Cheng C, Yang W, Cheok M, Wilkinson MR, Pei D et al. Lymphoid gene expression as a predictor of risk of secondary brain tumors. Genes Chromosomes and Cancer. 2005 Feb 1;42(2):107-116. https://doi.org/10.1002/gcc.20121
Edick, Mathew J. ; Cheng, Cheng ; Yang, Wenjian ; Cheok, Meyling ; Wilkinson, Mark R. ; Pei, Deqing ; Evans, William E. ; Kun, Larry E. ; Pui, Ching Hon ; Relling, Mary V. / Lymphoid gene expression as a predictor of risk of secondary brain tumors. In: Genes Chromosomes and Cancer. 2005 ; Vol. 42, No. 2. pp. 107-116.
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