LOSS OF HETEROZYGOSITY INVOLVING THE APC TUMOR SUPPRESSOR GENE IN HUMAN COLORECTAL CARCINOMA

To investigate whether aberration of the APC gene play any role in the development of Chinese sporadic colorectal carcinomas,we used a polymorphic site located in exon 11 which creted a new restriction site for RsaI to analyze LOH for the APC gene.We found that 20/29(68.9%) patients with colorectal cancer were informative for the APC exon 11 site and loss of one allele was detected in 40% of 20 informativc cascs.These data suggested that loss of heterozygosity of APC gene(APC-LOH) play a role in the pathogenesis of Chinese colorectal cancer.APC-LOH is a earlier event of colorectal tumorigenesis and may be of diagnostic value in Patient suffering colorectal cancer.

Analysis of two single nucleotide polymorphisms and loss of heterozygosity detection in the VHL gene in Chinese patients with sporadic renal cell carcinoma

Renal cell carcinoma （RCC） is the most common malignant tumour in the adult kidney. Recent studies have shown that inactivation of the tumour suppressor gene VHL located in chromosome 3p25-26 region is responsible for sporadic RCCs. According to Kundson＇s two hit theory, the mechanism of inactivation of a tumour suppressor gene involves mutation, hypermethylation and loss of heterozygosity （LOH）.

Detailed deletion mapping of loss of heterozygosity on 9p13-23 in laryngeal squamous cell carcinoma by microsatellite analysis

Background This study was designed to investigate the hot spots of microsatellite loss of heterozygosity (LOH) on 9p13-23 in laryngeal squamous cell carcinoma and to find out the correlation between the incidence of microsatellite LOH and the clinicopathological parameters Methods Tumor tissues were obtained from paraffin embedded sections with microdissection Genomic DNA was extracted from tumor tissues and peripheral blood lymphocytes with the phenol-chloroform Polymerase chain reaction (PCR) amplification and denaturing gel electrophoresis were carried out in a set of 42 squamous cell carcinoma (SCC) of larynx and corresponding peripheral blood lymphocytes using 13 highly polymorphic microsatellite markers on 9p13-23 The correlation was analyzed between microsatellite LOH at the high frequency on 9p13-23 and clinicopathological parameters in the patients with squamous cell carcinoma of larynx KH*2/5DResults Of the 42 laryngeal cancers, 41 (97 6%) showed LOH in at least one of the microsatellite markers tested on 9p13-23 The most frequently deleted marker was D9S162 in 17 of the 19 (89 5%) informative samples The marker D9S171, which is located on 9p21, had LOH detected in 12 of the 15 informative cases (80 0%) LOH at the D9S1748 marker (closest to the p16 gene locus) was detected in 18 of the 36 informative cases (50 0%) Allelic deletion mapping revealed two minimal regions of LOH encompassing markers D9S161-D9S171 on 9p21 and IFNA-D9S162 on 9p22-23 Multiple LOH (≥4) on 9p21-23 was found more frequently in the patients under 60 years, with supraglottic SCC or cervical lymph node metastasis than those over 60 years, with glottic SCC or without cervical lymph node metastasis ( P <0 01 or 0 01, 0 05, respectively) On the contrary, there was no correlation between T stages or pathologic classification and the frequency of LOH on 9p21-23 in 42 SCC of Larynx Conclusions These findings imply the presence of at least two putative tumor suppressor genes on 9p13-23 in laryngeal SCC Multiple genetic alterations are probably implicated in supraglottic SCC with cervical lymph node metastasis in younger patients

Genome-wide allelotype study of primary glioblastoma multiforme

To investigate the molecular genetic pathogenesis of primary glioblastoma multiforme (GBM) and identify which chromosomes or chromosomal regions of the entire genome may harbor tumor suppressor genes (TSGs) associated with GBM Methods A high-resolution allelotype study of 21 cases of primary GBM was performed by PCR-based loss of heterozygosity (LOH)analysis Three hundred and eighty-two fluorescent dye-labeled microsatellite markers covering all 22 autosomes were applied The mean genetic distance between two flanking markers was about 10 cM Results LOH was observed on all 39 nonacrocentric autosomal arms examined in this study The LOH frequencies of 10q, 10p, 9p, 17p and 13q were the highest (>50%) Furthermore, high LOH frequencies were detected in the regions containing known TSGs including PTEN, DMBT1, p16, p15, p53 and RB; the LOH frequencies on 14q, 3q, 22q, 11p, 9q, 19q were also high (>40 5%) Our study observed the following commonly deleted regions: 9p22-23, 10p12 2-14, 10q21 3, 13q12 1-14 1, 13q14 3-31, 17p11 2-12, 17p13, 3q25 2-26 2, 11p12-13, 14q13-31, 14q32 1, 14q11 1-13, 22q13 3, 4q35, 4q31 1-31 2, 6q27 and 6q21-23 3 Conclusions The molecular pathogenesis of GBM is very complicated and associated with a variety of genetic abnormalities on many chromosomal arms The most closely related chromosomal arms to the pathogenesis of GBM are 10q, 10p, 9p, 17p and 13q Besides the well-known TSGs including PTEN, DMBT1, p16, p15, p53 and RB, multiple unknown TSGs associated with GBM may be present on the commonly deleted regions detected in the present study