Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues

Xijin Ge, Shogo Yamamoto, Shuichi Tsutsumi, Yutaka Midorikawa, Sigeo Ihara, San Ming Wang, Hiroyuki Aburatani

Research output: Contribution to journalArticle

208 Scopus citations

Abstract

A critical and difficult part of studying cancer with DNA microarrays is data interpretation. Besides the need for data analysis algorithms, integration of additional information about genes might be useful. We performed genome-wide expression profiling of 36 types of normal human tissues and identified 2503 tissue-specific genes. We then systematically studied the expression of these genes in cancers by reanalyzing a large collection of published DNA microarray datasets. We observed that the expression level of liver-specific genes in hepatocellular carcinoma (HCC) correlates with the clinically defined degree of tumor differentiation. Through unsupervised clustering of tissue-specific genes differentially expressed in tumors, we extracted expression patterns that are characteristic of individual cell types, uncovering differences in cell lineage among tumor subtypes. We were able to detect the expression signature of hepatoctyes in HCC, neuron cells in medulloblastoma, glia cells in glioma, basal and luminal epithelial cells in breast tumors, and various cell types in lung cancer samples. We also demonstrated that tissue-specific expression signatures are useful in locating the origin of metastatic tumors. Our study shows that integration of each gene's breadth of expression (BOE) in normal tissues is important for biological interpretation of the expression profiles of cancers in terms of tumor differentiation, cell lineage, and metastasis.

Original languageEnglish (US)
Pages (from-to)127-141
Number of pages15
JournalGenomics
Volume86
Issue number2
DOIs
StatePublished - Aug 2005

Keywords

  • BRCA1
  • Breadth of expression
  • DNA microarray data interpretation
  • ESR1
  • Tissue-specific gene
  • Tumor differentiation

ASJC Scopus subject areas

  • Genetics

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    Ge, X., Yamamoto, S., Tsutsumi, S., Midorikawa, Y., Ihara, S., Wang, S. M., & Aburatani, H. (2005). Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics, 86(2), 127-141. https://doi.org/10.1016/j.ygeno.2005.04.008