Chromosomal alterations in lung adenocarcinoma from smokers and nonsmokers

Montserrat Sanchez-Cespedes, Steven A. Ahrendt, Steven Piantadosi, Rafael Rosell, Maria Monzo, Li Wu, William H. Westra, Stephen C Yang, Jin Jen, David Sidransky

Research output: Contribution to journalArticle

Abstract

The etiology of lung tumors arising in nonsmokers remains unclear. Although mutations in the K-ras and p53 genes have been reported to be significantly higher in smoking-related lung carcinomas, in the present study we performed a more comprehensive analysis in search of additional genetic changes between lung adenocarcinoma from tobacco- and non-tobacco-exposed patients. We selected a matched cohort of 18 lifetime nonsmoking and 27 smoking patients diagnosed with primary adenocarcinoma of the lung and searched for chromosomal alterations in each tumor by testing normal and tumor tissue with 54 highly polymorphic microsatellite markers located on 28 different chromosomal arms. Allelic losses or gains at chromosomal arms 3p (37 versus 6%), 6q (46 versus 12%), 9p (65 versus 22%), 16p (28 versus 0%), 17p (45 versus 11%), and 19p (58 versus 16%) were present significantly more often in adenocarcinomas from smokers than from nonsmokers. Chromosomal arms showing allelic imbalance in lung tumors from nonsmokers were rare but occurred more often at 19q (22%), 12p (22%), and 9p (22%). The FAL (fractional allelic loss or gain) is defined as the percentage of chromosomal arm losses/gains among the total informative chromosomal arms. Tumors from smokers harbored higher levels of FAL (13 (48%) of 27 showed FAL ≥ 0.3) compared with the lung tumors from the nonsmoker patients (2 (11%) of 18 showed FAL ≥ 0.3; P = 0.02; odds ratio, 0.13; 95% confidence interval, 0.01-0.79). Our data demonstrate that widespread chromosomal abnormalities are frequent in lung adenocarcinoma from smokers, whereas these abnormalities are infrequent in such tumors arising in nonsmokers. These observations support the notion that lung cancers in nonsmokers arise through genetic alterations distinct from the common events observed in tumors from smokers.

Original languageEnglish (US)
Pages (from-to)1309-1313
Number of pages5
JournalCancer Research
Volume61
Issue number4
StatePublished - Feb 15 2001

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Neoplasms
Lung
Loss of Heterozygosity
Smoking
Allelic Imbalance
ras Genes
Adenocarcinoma of lung
p53 Genes
Chromosome Aberrations
Microsatellite Repeats
Tobacco
Lung Neoplasms
Adenocarcinoma
Odds Ratio
Confidence Intervals
Carcinoma
Mutation

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Sanchez-Cespedes, M., Ahrendt, S. A., Piantadosi, S., Rosell, R., Monzo, M., Wu, L., ... Sidransky, D. (2001). Chromosomal alterations in lung adenocarcinoma from smokers and nonsmokers. Cancer Research, 61(4), 1309-1313.

Chromosomal alterations in lung adenocarcinoma from smokers and nonsmokers. / Sanchez-Cespedes, Montserrat; Ahrendt, Steven A.; Piantadosi, Steven; Rosell, Rafael; Monzo, Maria; Wu, Li; Westra, William H.; Yang, Stephen C; Jen, Jin; Sidransky, David.

In: Cancer Research, Vol. 61, No. 4, 15.02.2001, p. 1309-1313.

Research output: Contribution to journalArticle

Sanchez-Cespedes, M, Ahrendt, SA, Piantadosi, S, Rosell, R, Monzo, M, Wu, L, Westra, WH, Yang, SC, Jen, J & Sidransky, D 2001, 'Chromosomal alterations in lung adenocarcinoma from smokers and nonsmokers', Cancer Research, vol. 61, no. 4, pp. 1309-1313.
Sanchez-Cespedes M, Ahrendt SA, Piantadosi S, Rosell R, Monzo M, Wu L et al. Chromosomal alterations in lung adenocarcinoma from smokers and nonsmokers. Cancer Research. 2001 Feb 15;61(4):1309-1313.
Sanchez-Cespedes, Montserrat ; Ahrendt, Steven A. ; Piantadosi, Steven ; Rosell, Rafael ; Monzo, Maria ; Wu, Li ; Westra, William H. ; Yang, Stephen C ; Jen, Jin ; Sidransky, David. / Chromosomal alterations in lung adenocarcinoma from smokers and nonsmokers. In: Cancer Research. 2001 ; Vol. 61, No. 4. pp. 1309-1313.
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abstract = "The etiology of lung tumors arising in nonsmokers remains unclear. Although mutations in the K-ras and p53 genes have been reported to be significantly higher in smoking-related lung carcinomas, in the present study we performed a more comprehensive analysis in search of additional genetic changes between lung adenocarcinoma from tobacco- and non-tobacco-exposed patients. We selected a matched cohort of 18 lifetime nonsmoking and 27 smoking patients diagnosed with primary adenocarcinoma of the lung and searched for chromosomal alterations in each tumor by testing normal and tumor tissue with 54 highly polymorphic microsatellite markers located on 28 different chromosomal arms. Allelic losses or gains at chromosomal arms 3p (37 versus 6{\%}), 6q (46 versus 12{\%}), 9p (65 versus 22{\%}), 16p (28 versus 0{\%}), 17p (45 versus 11{\%}), and 19p (58 versus 16{\%}) were present significantly more often in adenocarcinomas from smokers than from nonsmokers. Chromosomal arms showing allelic imbalance in lung tumors from nonsmokers were rare but occurred more often at 19q (22{\%}), 12p (22{\%}), and 9p (22{\%}). The FAL (fractional allelic loss or gain) is defined as the percentage of chromosomal arm losses/gains among the total informative chromosomal arms. Tumors from smokers harbored higher levels of FAL (13 (48{\%}) of 27 showed FAL ≥ 0.3) compared with the lung tumors from the nonsmoker patients (2 (11{\%}) of 18 showed FAL ≥ 0.3; P = 0.02; odds ratio, 0.13; 95{\%} confidence interval, 0.01-0.79). Our data demonstrate that widespread chromosomal abnormalities are frequent in lung adenocarcinoma from smokers, whereas these abnormalities are infrequent in such tumors arising in nonsmokers. These observations support the notion that lung cancers in nonsmokers arise through genetic alterations distinct from the common events observed in tumors from smokers.",
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