Clonal selection of adenocarcinoma of the lung as determined by loss of heterozygosity.
Although the most frequently altered oncogenes and tumor suppressor genes in non-small cell lung carcinoma (NSCLC) have been recognized, the exact mechanisms responsible for the progression and phenotypic expression of carcinoma, particularly adenocarcinoma of the lung are uncertain. Fifty-six cases of adenocarcinoma of the lung (11 bronchioloalveolar carcinoma [BAC], 25 stage 1, 20 stage 2) and paired 19 lymph node metastases (LNM) of stage 2 adenocarcinomas were analyzed for loss of heterozygosity (LOH). Analysis included a panel of 14 polymorphic microsatellite markers located on 1p, 3p, 5q, 9p, 10q, and 17p. LOH on chromosomes 1p (P = 0.0209) and 17p (P = 0.0274) was more frequently present in stage 1 adenocarcinomas than in BAC. There was no significant difference between BAC, stage 1 and stage 2 adenocarcinoma in the frequency of LOH at individual chromosomal arms. The pattern of LOH in LNM of stage 2 adenocarcinoma was similar to the primary tumor. Overall fractional allelic loss (FAL) was significantly different between BAC and stage 1 invasive adenocarcinoma (P = 0.0013), and it was significantly higher in stage 1 adenocarcinoma than in stage 2 adenocarcinoma (P = 0.0062) and their LNM (P = 0.0001). Stage 2 adenocarcinomas showed significantly higher overall FAL than their LNM (P = 0.022). Our study failed to identify a single target gene responsible for progression of lung adenocarcinoma. A trend towards lower overall FAL in advanced stage tumors and in their metastases suggests that clonal selection may play a role in lung adenocarcinoma progression.
Dacic
Sanja
S
Department of Pathology, Division of Anatomic Pathology, University of Pittsburgh Medical Center, Presbyterian University Hospital, 200 Lothrop Street, PUH A610.2, Pittsburgh, PA 15213, USA. dacics@upmc.edu
Finkelstein
Sydney D
SD
Yousem
Samuel A
SA
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002999:Clone Cells; D005260:Female; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics*; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008207:Lymphatic Metastasis / Q000235:genetics* / Q000473:pathology; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D016133:Polymerase Chain Reaction