Correlations of allelic imbalance of chromosome 14 with adverse prognostic parameters in 148 renal cell carcinomas

✍ Scribed by Christophe Béroud; Jean-Christophe Fournet; Cécile Jeanpierre; Dominique Droz; Raymonde Bouvier; Delphine Froger; Yves Chretien; Jean-Marie Marechal; Jean Weissenbach; Claudine Junlen

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: English
• Weight: 803 KB
• Volume: 17
• Category: Article
• ISSN: 1045-2257
• DOI: 10.1002/(sici)1098-2264(199612)17:4<215::aid-gcc3>3.0.co;2-6

✦ Synopsis

To investigate cumulative genetic alterations during development and progression of renal cell carcinoma (RCC), we examined DNAs that were isolated from 148 RCCs for allelic imbalance (Al) at four loci on chromosome arm 3p and at 26 loci on chromosome arm 14q by using polymorphic microsatellite markers and densitometric scanning. Because the analysis of solid tumor unbalanced rearrangements remains difficult due t o the large proportion of cells that infiltrate from the stroma, we developed a method for the detection and quantification of Al between control and tumor samples by using polymerase chain reaction (PCR) amplification of microsatellite markers. This technique allows detection down to 20% of contaminating cells with good accuracy. We detected Al on 3p and 14q in 57 and 28% of RCC, respectively. A comparison of genetic changes with clinicopathological data showed that, in marked contrast t o Al on 3p, A l on 14q was correlated significantly with the stage and grade of the tumors, with 56 and 58% of RCC in Stage IV and Grade 4, respectively, showing Al. Our results suggest that tumor suppressor genes on 3p, including the von Hippel-Lindau gene, may be involved in early steps of carcinogenesis in clear cell carcinoma and that Al on 14q may play an important role in the progression of clear cell and papillary chromophilic cell carcinomas. Loss of heterozygosity (LOH) on 14q may be a new prognostic factor in RCC. Despite the size of the series of tumors and the number of markers used, only rearrangements that involved the whole length of the long arm of chromosome 14 were observed in the present study. The localization of the putative tumor suppressor gene on 14q will require further investigation of RCC with structural rearrangements of I4q.