Frequency and prognostic evaluation of 3p21‐22 allelic losses in non‐small‐cell lung cancer

Abstract

Previous loss of heterozygosity (LOH) studies of chromosome 3p loci have displayed a 60% deletion frequency in non-small-cell lung cancers (NSCLC), as opposed to small-cell lung cancers, in which the 3p deletion is consistently found. However, the high stromal-cell admixture found in NSCLC and the use of the Southern-blot method lead to under-evaluation of this frequency. In this study, we used a very precise microdissection technique followed by PCR amplification of 6 3p21-22 polymorphic genomic sequences to analyze LOH in 86 NSCLC and in normal adjacent tissue. We found the sensitivity of the microdissection-PCR-based LOH technique higher than the sensitivity of the Southern-blot technique: 87% of the squamous-cell carcinomas and 84% of the large-cell undifferentiated carcinomas showed a clear LOH for a 3p21-22 locus. All doubly informative cases but 4 showed concordant deletion at all 3p21-22 loci. The analysis of 3p microsatellite sequences displayed only 2 cases of genomic instability, one of them also displaying features of tumoral heterogeneity as regards the instability genotype. Four carcinomas in situ adjacent to these NSCLC showed the same allelic profile as the invasive tumors. The only prognostic factors in this study were the disease stage and histology. The 3p21-22 deletion was not related to the stage of the disease and did not appear to be a significant prognostic factor of survival. 3p21 loss appears, so far, to be the most frequent and the earliest genetic alteration described in NSCLC, but does not seem to carry significant prognostic information in invasive tumors.

BAP1: a novel ubiquitin hydrolase which binds to the BRCA1 RING finger and enhances BRCA1-mediated cell growth suppression

“…The FLpter value was 0.27+0.02 corresponding to a localization for BAP1 at 3p21.2-p21.31. This location is a region of LOH for breast cancer as well as a region frequently deleted in lung carcinomas (Buchhagen et al, 1994;Thiberville et al, 1995).…”

Chromosome 3p24‐26 and 3p22‐12 loss in human prostatic adenocarcinoma

“…Chromosome 3 loci have display 60% deletion in nonsmall-cell lung carcinomas (Thiberville et al, 1995). Although 3p loss appears to be the most frequent and earliest genetic alteration in small-cell lung carcinoma, it does not correlate with progression of the disease (Thiberville et al, 1995).…”

Topographical distribution of allelic loss in individual lung adenocarcinomas with lymph node metastases

“…[26][27][28][29] Recent studies have suggested that the LOH at specific chromosomal loci, 1p, 3p, 5q, 9p, 17q, and 22q, is associated with a worse prognosis of NSCLC, although studies of patients from different populations have yielded conflicting results. 14,[30][31][32][33][34][35][36][37][38][39] LOH at the APC/MCC gene cluster at chromosome 5q has been reported to correlate with poorer survival of patients with NSCLC. 38 In the present study, the tumors were small but were associated with lymph node metastasis, and a worse prognosis was assumed.…”