Comparative genomic profiling by array of human carcinomas of unknown primary compared to classical secondary metastases

Carcinomas of unknown primary (CUP) are characterized by early metastatic dissemination in the absence of a detectable primary tumor. This disease accounts for about 3% of all malignant tumors. Most CUPs are poorly responsive to chemotherapy and have a rapid fatal evolution. The biological mechanisms supporting metastatic growth in various sites combined with regression or absence of growth in the primary site are still poorly understood. The aim of this project was to investigate structural genome alterations specifically detected by CGH-array in CUP but not in classical secondary metastases. The design of the project was as follows : 5 samples representative of CUPs were compared to 3 samples representative of classical secondary metastases. The CUP samples were : a) 3 fresh biopsies containing more than 60 % malignant cells on tissue sections adjacent to the tumor fragment used for DNA extraction (Gal., Pro., Gag.); b) 2 fragment derived from 2 xenografted CUP tumor lines, Capi 1 and Capi 3 respectively. The samples derived from classical secondary metastases were : a) one fresh biopsy fragment derived from the secondary metastasis of a rectal adenocarcinoma (Vuc.); b) fragments of a tumor resulting from a xenograft of Capan 1, an in vitro cell line derived from a pancreatic adenocarcinoma secondary metastasis; 3) fragments of a xenografted tumor derived from a lung adenocarcinoma metastasis called IC14 (NSCLC).