Browsing by Author "Tang, MY"

Now showing 1 - 2 of 2
  • Thumbnail Image
    Item
    Genome-wide allelotyping analysis reveals multiple sites of allelic loss in gallbladder carcinoma
    (AMER ASSOC CANCER RESEARCH, 2001) Wistuba, II; Tang, MY; Maitra, A; Alvarez, H; Troncoso, P; Pimental, F; Gazdar, AF
    Although gallbladder carcinoma (GBC) is a highly malignant neoplasm, there is very limited information about the molecular changes involved in its pathogenesis. To identify the chromosomal locations of putative tumor suppressor gene loci Involved in the pathogenesis of GBC, we conducted a genome-wide allelotyping or loss of heterozygosity (LOH) analysis of GBCs. Microdissected tissue from 24 archival GBCs and their matched control DNAs were analyzed for PCR-based LOH using 169 microsatellite markers spanning all nonacrocentric autosomal arms and the X chromosome. The chromosomal arms with the greatest frequencies of LOH (greater than or equal to 60%) were 3p, 6q, 7q, 8p, 9p, 9q, 11q, 12q, 17p, 18q, 19p, 22q, and Xq. The average fractional allele loss index in GBC cases was high (0.43) and frequent breakpoints were detected in gallbladder tumors. Of interest, 21 different regions of frequent LOH (hot spots) defined as greater than or equal to 50% for individual GBC samples were detected in this neoplasm, nearly half of them confined to one microsatellite marker. We conclude that in GBC at least 21 chromosomal regions with frequent allele losses are involved, suggesting that several putative tumor suppressor genes are inactivated in its pathogenesis. Overall, these data provide global estimates of the extent of genetic changes leading to GBC and will be useful for the identification of new tumor suppressor genes and for multiple new markers for translational research.
  • No Thumbnail Available
    Item
    Microsatellite analysis of synchronous and metachronous tumors - A tool for double primary tumor and metastasis assessment
    (2003) Tang, MY; Pires, Y; Schultz, M; Duarte, I; Gallegos, M; Wistuba, II
    Despite well-established histopathological features and the development of immunostaining of human neoplasms, there are a number of cases in which surgical pathologists cannot assure the origin of synchronous and metachronous tumors. In many cases, the classification of these lesions as either two separate primary tumors or as a single primary tumor with a metastasis has significant implications with respect to patient prognosis and recommendations for therapy. To establish the origin of tumors, we assessed tumor cell clonality using PCR-based microsatellite analysis on microdissected archival tissues for loss of heterozygosity (LOH) and microsatellite instability (NISI) in a series of 19 paired synchronous and metachronous tumors from several organs. As a control group, 15 autopsy cases with an unequivocally recognizable primary tumor and associated metastases were also examined. Based on LOH and MSI findings, and using a panel of 4 to 12 (median 7) microsatellite markers, we were able to establish the clonal pattern of microsatellite changes in 17 out of 19 (89%) biopsy cases and thus determine if they were either double primary tumors (41%) or metastases (59%). Of interest, identical or similar pattern of microsatellite abnormalities were detected in 15 primary tumors and corresponding metastasis from autopsies. Our results indicate that microsatellite analysis for LOH and MSL as an expression of clonality, provides a useful tool to distinguish double primary neoplasms and metastases in synchronous and metachronous tumors.