PURPOSE: Loss of various loci on chromosome 9 has been reported in various cancers. To determine the frequency of deletions at different loci of chromosome 9 in renal cell carcinoma microdissected samples of normal renal epithelium and carcinoma from the same patients were analyzed. MATERIALS AND METHODS: DNA was isolated from microdissected sections of normal and tumor cells of 60 renal specimens, amplified by polymerase chain reaction and analyzed for loss of heterozygosity on chromosome 9 using the 16 microsatellite markers D9S178, D9S157, D9S274, D9S168, D9S285, D9S156, D9S1839, D9S162, IFNA, D9S736, D9S171, D9S1749, D9S273D9S270, D9S153 and D9S170. Loss of heterozygosity was analyzed by a polymerase chain reaction based technique developed at our laboratory. RESULTS: This study showed a high incidence of loss of heterozygosity on chromosome 9 in renal cell carcinoma. Of 60 cases 44 (73%), 24 (40%) and 14 (23%) showed loss of heterozygosity at a minimum of 1, at a minimum of 3 and at 4 or more loci, respectively. The main deletion was found on the 9p21 region at loci DS171 in 38% of cases, D9S1749 in 42% and DS270 in 14%. Overall deletion on chromosome 9p21 was noted in 57% of renal cancer cases. Other deleted regions were on chromosome 9p'0022 to 23 at loci D9S157 in 37% of cases, D9S274 in 20%, D9S168 in 27%, D9S285 in 20%, D9S156 in 12%, D9S1839 in 17% and D9S162 in 24%. Overall deletion at chromosome 9q32 to 33 was noted in 46% of renal cell carcinoma cases. Chromosome 9q32 to 33 also showed deletion at locus D9S170 in 22% of renal cell carcinoma cases. When we compared the incidence of deletion at various loci on chromosome 9 according to renal cell carcinoma grade, we found a higher rate of deletion in advanced grades of renal cell carcinoma. A candidate target tumor suppressor gene, p16 (MTS-1/CDKN2), has been identified within the 9p21 deleted region in various cancers. In our study the expression of p16 protein was absent or low in renal cell cancer samples, suggesting that loss of the p16 gene may be involved in renal cell carcinogenesis. CONCLUSIONS: Our study demonstrates a high incidence of loss of heterozygosity on chromosome 9, mainly 9p21 and 9p22 to 23, in renal cell carcinoma, suggesting several putative tumor suppressor genes on these regions. The identification of other tumor suppressor genes on the 9p21 and 9p22 to 23 regions warrants further studies.
PURPOSE: Loss of various loci on chromosome 9 has been reported in various cancers. To determine the frequency of deletions at different loci of chromosome 9 in renal cell carcinoma microdissected samples of normal renal epithelium and carcinoma from the same patients were analyzed. MATERIALS AND METHODS: DNA was isolated from microdissected sections of normal and tumor cells of 60 renal specimens, amplified by polymerase chain reaction and analyzed for loss of heterozygosity on chromosome 9 using the 16 microsatellite markers D9S178, D9S157, D9S274, D9S168, D9S285, D9S156, D9S1839, D9S162, IFNA, D9S736, D9S171, D9S1749, D9S273D9S270, D9S153 and D9S170. Loss of heterozygosity was analyzed by a polymerase chain reaction based technique developed at our laboratory. RESULTS: This study showed a high incidence of loss of heterozygosity on chromosome 9 in renal cell carcinoma. Of 60 cases 44 (73%), 24 (40%) and 14 (23%) showed loss of heterozygosity at a minimum of 1, at a minimum of 3 and at 4 or more loci, respectively. The main deletion was found on the 9p21 region at loci DS171 in 38% of cases, D9S1749 in 42% and DS270 in 14%. Overall deletion on chromosome 9p21 was noted in 57% of renal cancer cases. Other deleted regions were on chromosome 9p'0022 to 23 at loci D9S157 in 37% of cases, D9S274 in 20%, D9S168 in 27%, D9S285 in 20%, D9S156 in 12%, D9S1839 in 17% and D9S162 in 24%. Overall deletion at chromosome 9q32 to 33 was noted in 46% of renal cell carcinoma cases. Chromosome 9q32 to 33 also showed deletion at locus D9S170 in 22% of renal cell carcinoma cases. When we compared the incidence of deletion at various loci on chromosome 9 according to renal cell carcinoma grade, we found a higher rate of deletion in advanced grades of renal cell carcinoma. A candidate target tumor suppressor gene, p16 (MTS-1/CDKN2), has been identified within the 9p21 deleted region in various cancers. In our study the expression of p16 protein was absent or low in renal cell cancer samples, suggesting that loss of the p16 gene may be involved in renal cell carcinogenesis. CONCLUSIONS: Our study demonstrates a high incidence of loss of heterozygosity on chromosome 9, mainly 9p21 and 9p22 to 23, in renal cell carcinoma, suggesting several putative tumor suppressor genes on these regions. The identification of other tumor suppressor genes on the 9p21 and 9p22 to 23 regions warrants further studies.
Authors: Wen-Qing Li; Ruth M Pfeiffer; Paula L Hyland; Jianxin Shi; Fangyi Gu; Zhaoming Wang; Samsiddhi Bhattacharjee; Jun Luo; Xiaoqin Xiong; Meredith Yeager; Xiang Deng; Nan Hu; Philip R Taylor; Demetrius Albanes; Neil E Caporaso; Susan M Gapstur; Laufey Amundadottir; Stephen J Chanock; Nilanjan Chatterjee; Maria Teresa Landi; Margaret A Tucker; Alisa M Goldstein; Xiaohong R Yang Journal: Carcinogenesis Date: 2014-09-19 Impact factor: 4.944
Authors: Seyed Ali Hosseini; Susan Horton; Joshua C Saldivar; Satoshi Miuma; Martha R Stampfer; Nyla A Heerema; Kay Huebner Journal: Genes Chromosomes Cancer Date: 2013-08-09 Impact factor: 5.006
Authors: Helena Nord; Christian Hartmann; Robin Andersson; Uwe Menzel; Susan Pfeifer; Arkadiusz Piotrowski; Adam Bogdan; Wojciech Kloc; Johanna Sandgren; Tommie Olofsson; Göran Hesselager; Erik Blomquist; Jan Komorowski; Andreas von Deimling; Carl E G Bruder; Jan P Dumanski; Teresita Díaz de Ståhl Journal: Neuro Oncol Date: 2009-12 Impact factor: 12.300
Authors: Ismail El-Mokadem; John Fitzpatrick; Bhavan Rai; J Cunningham; Norman Pratt; Stewart Fleming; Ghulam Nabi Journal: Biomed Res Int Date: 2014-04-30 Impact factor: 3.411
Authors: I El-Mokadem; J Fitzpatrick; J Bondad; P Rauchhaus; J Cunningham; N Pratt; S Fleming; G Nabi Journal: Br J Cancer Date: 2014-08-19 Impact factor: 7.640
Authors: Ning Yi Yap; Retnagowri Rajandram; Keng Lim Ng; Jayalakshmi Pailoor; Ahmad Fadzli; Glenda Carolyn Gobe Journal: Biomed Res Int Date: 2015-09-13 Impact factor: 3.411
Authors: Ismail El-Mokadem; Alison Lim; Thomas Kidd; Katherine Garret; Norman Pratt; David Batty; Stewart Fleming; Ghulam Nabi Journal: BMC Cancer Date: 2016-07-27 Impact factor: 4.430