Chromosomal aberrations of primary lung adenocarcinomas in nonsmokers.
BACKGROUND
Lung carcinoma is a common malignancy, and tobacco carcinogenesis is the major cause. Studies on individual genes or loci have suggested, that in tumors from nonsmokers, different genetic alterations are present compared with tumors from smokers. It is possible that distinct genetic pathways may be involved. However, the targets remain largely unknown; and, to the authors' knowledge, molecular cytogenetics studies on lung carcinomas from nonsmokers have not been reported.


METHODS
Comparative genomic hybridization (CGH) analysis was performed on primary lung adenocarcinoma samples from 32 patients who never smoked to identify loci of frequent aberrations.


RESULTS
Different extents of aberration were found in 31 of the 32 samples studied. The most frequently altered locus was gain of 16p (59% of samples) followed by gain of 20q (44% of samples), with the minimal overlapping regions at 16p13.1-p13.2 and 20q13.2, respectively. Other over-represented loci with > 30% frequency were observed at 5p (34% of samples), 7p (41% of samples), 8q (31% of samples), 17q (34% of samples), and 19q (34% of samples); and high-level DNA amplifications were detected at 1q, 7p, 12q, 19q, and 20q. DNA under-representation was observed less commonly and included 8p (28% of samples), 9p (22% of samples), 13q (28% of samples), and 18q (38% of samples).


CONCLUSIONS
The current study identified targets of frequent genetic aberration in primary adenocarcinomas from nonsmokers. Compared with reported CGH findings in the literature, the current findings suggest that DNA gain at 16p is the distinct aberration involved in these tumors. Other frequently altered loci involve commonly reported oncogenic and tumor suppressor loci, suggesting an overlap with the genetic pathways of tobacco-induced lung carcinogenesis.
Wong
Maria P
MP
Department of Pathology, The University of Hong Kong, Hong Kong, China.
Fung
Lai-Fan
LF
Wang
Elaine
E
Chow
Wing-Shun
WS
Chiu
Shui-Wah
SW
Lam
Wah-Kit
WK
Ho
Kwok-Keung
KK
Ma
Edmond S K
ES
Wan
Thomas S K
TS
Chung
Lap-Ping
LP
D000230:Adenocarcinoma / Q000235:genetics*; D000328:Adult; D000368:Aged; D002869:Chromosome Aberrations; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics*; D004273:DNA, Neoplasm / Q000032:analysis*; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009693:Nucleic Acid Hybridization; D012907:Smoking / Q000009:adverse effects / Q000235:genetics
D004273:DNA, Neoplasm