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

ABSTRACT: 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).

ORGANISM(S): Homo sapiens

SUBMITTER: ripoche unknown

PROVIDER: S-ECPF-TABM-1057 | biostudies-other |

REPOSITORIES: biostudies-other

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Project description:We designed a study to investigate genetic relationships between primary tumors of oral squamous cell carcinoma (OSCC) and their lymph node metastases, and to identify genomic copy number aberrations (CNAs) related to lymph node metastasis. For this purpose, we collected a total of 42 tumor samples from 25 patients and analyzed their genomic profiles by array-based comparative genomic hybridization. We then compared the genetic profiles of metastatic primary tumors (MPTs) with their paired lymph node metastases (LNMs), and also those of LNMs with non-metastatic primary tumors (NMPTs). Firstly, we found that although there were some distinctive differences in the patterns of genomic profiles between MPTs and their paired LNMs, the paired samples shared similar genomic aberration patterns in each case. Unsupervised hierarchical clustering analysis grouped together 12 of the 15 MPT-LNM pairs. Furthermore, similarity scores between paired samples were significantly higher than those between non-paired samples. These results suggested that MPTs and their paired LNMs are composed predominantly of genetically clonal tumor cells, while minor populations with different CNAs may also exist in metastatic OSCCs. Secondly, to identify CNAs related to lymph node metastasis, we compared CNAs between grouped samples of MPTs and LNMs, but were unable to find any CNAs that were more common in LNMs. Finally, we hypothesized that subpopulations carrying metastasis-related CNAs might be present in both the MPT and LNM. Accordingly, we compared CNAs between NMPTs and LNMs, and found that gains of 7p, 8q and 17q were more common in the latter than in the former, suggesting that these CNAs may be involved in lymph node metastasis of OSCC. In conclusion, our data suggest that in OSCCs showing metastasis, the primary and metastatic tumors share similar genomic profiles, and that cells in the primary tumor may tend to metastasize after acquiring metastasis-associated CNAs.

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

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