Molecular Signatures of gastric cancer: An integrated approach to molecular cytogenetics, whole genome copy number and transcriptome profiles
Signature chromosomal translocations in gastric cancer are poorly described. By integrating spectral karyotype and high-resolution genome copy number data, 45 recurrent translocations in 17 human gastric cancer cell lines were identified. Dissecting a simple rearrangement in SNU-1 cells using fluorescence in situ hybridization probe-walking confirmed a 4q32.3q35.1 deletion associated with three chromosomal fusions. Among complex rearrangements, 18q21 was most frequently aberrant (35% of cell lines) with multiple fusion partners and sustained copy number loss in >50%. This 18q21q22 translocation was mirrored in 38% of 99 primary gastric cancer adenocarcinomas. High resolution analysis of flow-sorted rearranged chromosome 18 species from four cell lines identified fusion partners and probable breakpoints. Translocation-positive and -negative lines segregated distinctly in supervised hierarchical clustering of 18q genes. Immunohistochemical staining of 18q proteins, Serpin B8 and CD226 antigen, showed overexpression in breakapart-positive primary gastric cancers. Other molecular signatures from whole genome copy number, mRNA and miRNA profiles are described.
Gastric cancer, Molecular signatures, cytogenetics, copy number, transcriptome
Networked Digital Library of Theses and Dissertations