Loss of chromosome arms 3p and 9p and inactivation of P16INK4a in normal epithelium of patients with primary lung cancer

Otávia L. Caballero, Daniel Cohen, Qing Liu, Manel Esteller, Julie Bonacum, Peter White, James Engles, Robert Yochem, James G. Herman, William H. Westra, Christoph Lengauer, David Sidransky, Jin Jen

Research output: Contribution to journalArticle

Abstract

The accumulation of genetic alterations in the respiratory epithelium may give rise to cancer and often is accompanied by a series of histologic alterations over a period of several years. Recent studies have identified some molecular alterations in histologically normal-appearing epithelium among patients with lung cancer. To extend these observations, we investigated clonal genetic alterations by using fluorescence in situ hybridization (FISH) analysis and immunohistochemistry in 69 biopsy samples of histogically normal-appearing bronchial epithelium from 22 patients with or without lung cancer. Thirty-seven biopsy specimens from 13 patients were examined for loss of 3p14, and 48 biopsy specimens from 18 patients were examined for loss at 9p21 by FISH. P16INK4a expression was analyzed in 54 biopsy samples from 19 patients. In at least one biopsy specimen from five of the 13 patients with primary lung cancer, FISH or immunohistochemistry detected loss of the 3p14 or 9p21 region. In contrast, no alterations were detected for the same regions in the nine patients without primary lung cancer. Our results support the concept that the normal epithelial surface of large bronchi of patients with lung cancer has molecular changes suggestive of the outgrowth of numerous clonal foci.

Original languageEnglish (US)
Pages (from-to)119-125
Number of pages7
JournalGenes Chromosomes and Cancer
Volume32
Issue number2
DOIs
StatePublished - Sep 26 2001

ASJC Scopus subject areas

  • Genetics
  • Cancer Research

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    Caballero, O. L., Cohen, D., Liu, Q., Esteller, M., Bonacum, J., White, P., Engles, J., Yochem, R., Herman, J. G., Westra, W. H., Lengauer, C., Sidransky, D., & Jen, J. (2001). Loss of chromosome arms 3p and 9p and inactivation of P16INK4a in normal epithelium of patients with primary lung cancer. Genes Chromosomes and Cancer, 32(2), 119-125. https://doi.org/10.1002/gcc.1173