Molecular changes in the bronchial epithelium of patients with small cell lung cancer

Ignacio I. Wistuba, Jarett Berry, Carmen Behrens, Anirban Maitra, Narayan Shivapurkar, Sara Milchgrub, Bruce Mackay, John D. Minna, Adi F. Gazdar

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Abstract

To better understand the pathways involved in the pathogenesis of small cell lung carcinoma (SCLC), we compared the patterns of molecular changes present in these tumors and their accompanying bronchial epithelium with those present in the other two major types of lung cancer [squamous cell carcinoma (SQC) and adenocarcinoma (ADC)]. We obtained DNA from 68 microdissected invasive lung tumors (22 SCLCs, 21 ADCs, and, 25 SQCs) and 119 noncontiguous foci of histologically normal or hyperplastic epithelia from 10 tumors of each histological type. We determined loss of heterozygosity and microsatellite alterations at 12 chromosomal regions frequently deleted in lung cancers using 19 polymorphic microsatellite markers. Our major findings are as follows: (a) the mean index of allelic loss in SCLC (0.85) and SQC (0.71) tumors was higher than that in ADC (0.39) tumors; (b) although there was considerable overlap, each tumor type had a characteristic pattern of allelic loss; (c) most samples of bronchial epithelium accompanying SCLC (90%) had allelic loss at one or more loci compared with samples accompanying SQC (54%) or ADC (10%); (d)-the mean index of allelic loss was much higher in bronchial epithelial samples from SCLC (0.27) than in those from SQC (0.08) or ADC (0.01); and (e) although the mean indices of microsatellite alterations in the tumor types were similar, the bronchial epithelial samples accompanying SCLC had a 10-fold higher mean index (0.063) than those accompanying SQC (0.006) or ADC (0.006). Our findings indicate that extensive genetic damage in the accompanying normal and hyperplastic bronchial epithelium is characteristic of SCLC tumors and suggest major differences in the pathogenesis of the three major lung cancer types.

Original languageEnglish (US)
Pages (from-to)2604-2610
Number of pages7
JournalClinical Cancer Research
Volume6
Issue number7
StatePublished - Jul 2000

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Small Cell Lung Carcinoma
Epithelium
Loss of Heterozygosity
Squamous Cell Carcinoma
Adenocarcinoma
Neoplasms
Microsatellite Repeats
Lung Neoplasms
Lung
DNA

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Molecular changes in the bronchial epithelium of patients with small cell lung cancer. / Wistuba, Ignacio I.; Berry, Jarett; Behrens, Carmen; Maitra, Anirban; Shivapurkar, Narayan; Milchgrub, Sara; Mackay, Bruce; Minna, John D.; Gazdar, Adi F.

In: Clinical Cancer Research, Vol. 6, No. 7, 07.2000, p. 2604-2610.

Research output: Contribution to journalArticle

Wistuba, Ignacio I. ; Berry, Jarett ; Behrens, Carmen ; Maitra, Anirban ; Shivapurkar, Narayan ; Milchgrub, Sara ; Mackay, Bruce ; Minna, John D. ; Gazdar, Adi F. / Molecular changes in the bronchial epithelium of patients with small cell lung cancer. In: Clinical Cancer Research. 2000 ; Vol. 6, No. 7. pp. 2604-2610.
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abstract = "To better understand the pathways involved in the pathogenesis of small cell lung carcinoma (SCLC), we compared the patterns of molecular changes present in these tumors and their accompanying bronchial epithelium with those present in the other two major types of lung cancer [squamous cell carcinoma (SQC) and adenocarcinoma (ADC)]. We obtained DNA from 68 microdissected invasive lung tumors (22 SCLCs, 21 ADCs, and, 25 SQCs) and 119 noncontiguous foci of histologically normal or hyperplastic epithelia from 10 tumors of each histological type. We determined loss of heterozygosity and microsatellite alterations at 12 chromosomal regions frequently deleted in lung cancers using 19 polymorphic microsatellite markers. Our major findings are as follows: (a) the mean index of allelic loss in SCLC (0.85) and SQC (0.71) tumors was higher than that in ADC (0.39) tumors; (b) although there was considerable overlap, each tumor type had a characteristic pattern of allelic loss; (c) most samples of bronchial epithelium accompanying SCLC (90{\%}) had allelic loss at one or more loci compared with samples accompanying SQC (54{\%}) or ADC (10{\%}); (d)-the mean index of allelic loss was much higher in bronchial epithelial samples from SCLC (0.27) than in those from SQC (0.08) or ADC (0.01); and (e) although the mean indices of microsatellite alterations in the tumor types were similar, the bronchial epithelial samples accompanying SCLC had a 10-fold higher mean index (0.063) than those accompanying SQC (0.006) or ADC (0.006). Our findings indicate that extensive genetic damage in the accompanying normal and hyperplastic bronchial epithelium is characteristic of SCLC tumors and suggest major differences in the pathogenesis of the three major lung cancer types.",
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AU - Berry, Jarett

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AU - Shivapurkar, Narayan

AU - Milchgrub, Sara

AU - Mackay, Bruce

AU - Minna, John D.

AU - Gazdar, Adi F.

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