Genetic analysis in desmoid tumors from patients with familial adenomatous polyposis

1735 Familial adenomatous polyposis (FAP) is characterized by the development of hundreds of adenomatous polyps in the colon and rectum. This disease is caused by germline mutations in the APC gene. Some FAP patients develop extracolonic tumors such as desmoid tumors. These tumors are the second cause of death in FAP patients. Genetic analysis of colonic tumors has shown specific gene alterations during the progression from normal mucosa to colorectal cancer. Nevertheless, there is scarce genetic knowledge about desmoid tumors. Our aims were 1) to determine the participation of specific genes in the development of desmoid tumors, and, 2) to determine chromosomal alterations in desmoid tumors allowing the identification of new genes. In this study, 6 biopsies of desmoid tumors were analyzed, looking for loss of heterozygosity (LOH) of APC, DCC and P53 genes through single strand conformation polymorphism technique (SSCP), DNA sequencing and amplification of STR markers. Furthermore, mutations in the oncogene k-ras were screened by DNA sequencing, and we analyzed the samples for chromosomal alterations by microarrays-comparative genomic hybridization (array-CGH). In this study, no LOH in the APC, DCC and P53 genes was found, nor mutations in the oncogene k-ras, in contrast of the presence of these alterations in colorectal cancer. On the other hand, the analysis by array-CGH has allowed us to identify common chromosomal gains 1q12-1q23, 6p22-6p21, 8q21-8q24, 11p15, 11q12-11q13 and one main deletion 2q21-2q34 in the 6 desmoid tumors. These regions may contain tumor suppressor genes and oncogenes that could contribute to the development of these tumors. Supported by National Grant FONDECYT 1040827