No abstract

To investigate the genomic aberrations that are involved in lung tumorigenesis and therefore may be developed as biomarkers for lung cancer diagnosis, we characterized the genomic copy number changes associated with individual genes in 14 tumors from patients with primary non small cell lung cancer (NSCLC). Six squamous cell carcinomas (SQCAs) and eight adenocarcinomas (ADCAs) were examined by high-resolution comparative genomic hybridization (CGH) analysis of cDNA microarray. The SQCAs and ADCAs shared common frequency distributions of recurrent genomic gains of 63 genes and losses of 72 genes. Cluster analysis using 57 genes defined the genomic differences between these two major histologic types of NSCLC. Genomic aberrations from a set of 18 genes showed distinct difference of primary ADCAs from their paired normal lung tissues. The genomic copy number of four genes was validated by fluorescence in situ hybridization of 32 primary NSCLC tumors, including those used for cDNA microarray CGH analysis; a strong correlation with cDNA microarray CGH data emerged. The identified genomic aberrations may be involved in the initiation and progression of lung tumorigenesis and, most importantly, may be developed as new biomarkers for the early detection and classification of lung cancer.

We studied loss of heterozygosity (LOH) on human chromosome 13q in prostate cancer specimens to determine the location of a putative tumor suppressor gene (TSG) and to correlate these losses with the clinicopathological stage of the disease. Overall 13 (21%) of 61 specimens analysed had an allele loss on the long arm of chromosome 13. The most frequent (37%) LOH among the informative cases with allele losses was detected at the D13S284 locus on chromosome 13q14.3. A portion of the DNA segment that spans this locus and is¯anked by the microsatellite loci D13S153 and D13S163 was lost in 85% of the specimens with allele losses and was designated as a LOH cluster region (LCR). The LCR spans more than 6 Mbp of DNA. The results suggest that a TSG relevant for the development of prostate cancer is located telomeric to the RB locus. There was a signi®cant correlation (P=0.0024) between chromosome 13q LOH and advanced metastatic disease, suggesting that loss of 13q14.3 region is associated with prostate cancer progression. However, further research must be conducted to establish the identity and function of this putative TSG.

We studied loss of heterozygosity (LOH) on the long arm of human chromosome 18 in prostate cancer to determine the location of a putative tumor suppressor gene (TSG) and to correlate these losses with the pathological grade and stage of the cancer. Of 48 specimens analysed 17 (35.4%) lost at least one allele on chromosome 18q. All the specimens with allelic losses lost at least one allele within chromosomal region 18q21. Allelic losses picked at D18S51 (19%) and D18S858 (17%). A 0.58 cM DNA segment that includes the D18S858 locus and is¯anked by the microsatellite loci D18S41 and D18S381, was lost in eight (47%) of 17 specimens with allelic losses. This segment was designated as a LOH cluster region 1 (LCR 1). Although Smad2 resides within LCR 1, it was not mutated in any of the six prostate cell lines (®ve prostate cancer cell lines and one immortalized prostate epithelial cell line) analysed, suggesting that it is not a candidate TSG in prostate cancer. A second LCR at 18q21, LCR 2, includes the D18S51 locus and is¯anked by the D18S1109 and D18S68 loci, which are separated by 7.64 cM. LCR 2 was lost in six (35%) of the 17 specimens with chromosome 18q losses. These results suggest that chromosome 18q21 may harbor two candidate prostate cancer TSGs. The candidate TSGs DCC and Smad4 are located centromeric to the LCRs. No alleles were lost within or in close proximity to these genes, suggesting that they are not targets for inactivation by allelic losses in prostate cancer. Although there was no obvious correlation between chromosome 18q LOH and the pathological grade or stage, three (37.5%) of eight low-grade cancers and nine (32.1%) of 28 organcon®ned cancers lost alleles at 18q21, suggesting that allelic losses are relatively early events in the development of invasive prostate cancer. Oncogene (2001) 20, 2273 ± 2280.