Frequency and extent of allelic loss in the short arm of chromosome 3 in nonsmall‐cell lung cancer

Abstract

DNA was prepared from tumour and normal tissue from 48 patients representing all common histological types of nonsmall-cell lung cancer. Using eight DNA probes, which detect nine restriction enzyme fragment length polymorphisms (RFLP) on chromosome 3, we established that among the 44 informative patients 32 had lost alleles on the short arm of one of their copies of chromosome 3. Of these 32, at least 13 had also lost alleles on the long arm of chromosome 3, suggesting that the whole chromosome might be lost. For one patient, cytogenetic analysis indicated that the mechanism of allelic loss was reciprocal translocation followed by chromosomal loss of one of the reciprocal products. Two patients with allelic loss distal to the D3S3 locus (which maps to 3p13-14) retained heterozygosity at that locus. These results indicate that loss of alleles on the short arm of chromosome 3 is a common event in lung tumours of the nonsmall-cell type, that this loss occurs by a variety of chromosomal mechanisms, and that the minimally deleted region is 3p13-14----3pter.

Cytogenetic analysis of 63 non‐small cell lung carcinomas: Recurrent chromosome alterations amid frequent and widespread genomic upheaval

“…Loss of all or part of 3p was identified in 75% of our NSCLCs. Loss of heterozygosity for alleles in 3p has been reported in 25-100% of NSCLCs in different reports (Brauch et al, 1987;Kok et al, 1987;Yokota et al, 1987;Rabbitts et al, 1989;Weston et al, 1989). In our tumors, the SRO of 3p losses appears to be at band p21.…”

Direct correlation between FRA3B expression and cigarette smoking

“…This model is consistent with the proposed tumor-suppressor activity of the FHIT gene that has been reported to be mu-tated in tumors caused by environmental carcinogens (Mori et al, 2000). In addition to being found in SCLC, chromosomal and molecular deletions and rearrangements with breaks at or near FRA3B have been identified in a variety of different malignancies including renal cell carcinoma, nonsmall cell lung cancer, nasopharyngeal carcinoma, and pancreatic cancer (Wang and Perkins, 1984;Rabbitts et al, 1989;Huang et al, 1991;Shridhar et al, 1996), further implicating fragile site expression in tumorigenesis. Therefore, the effect of environmental mutagens on fragile sites may play a role in disease processes including carcinogenesis.…”

Positional cloning of the hereditary renal carcinoma 3;8 chromosome translocation breakpoint.

“…The largest of these cDNA clones, K7, contains a 1.7-kb insert with a poly(A) tract. On Southern hybridization, the K7 probe detects the 3;8 translocation breakpoint on EcoRI digestion of DNA from the der (8) hybrid. This is shown in Fig.…”

“…In renal carcinoma, 3p involvement approaches 90o in the clear cell histologic variety (1)(2)(3)(4), while in smallcell lung cancer the loss is universal (5,6). In non-small-cell lung cancer, which includes squamous, adeno, and large cell histologies, 3p loss occurs in up to 75% of cases (7,8). In addition, 3p loss has been reported in 90-100%o of cervical cancers (9,10) and other frequent 3p losses have been described in thyroid, head and neck, breast, and testicular cancers (11)(12)(13)(14)(15) at the genomic level has been detected in studies that included a pulsed-field analysis extending 1 Mb in the direction of the translocation breakpoint (20).…”