title: Genomic profiling of submucosal-invasive gastric cancer by array-based comparative genomic hybridization.
abstract: Genomic copy number aberrations (CNAs) in gastric cancer have already been extensively characterized by array comparative genomic hybridization (array CGH) analysis. However, involvement of genomic CNAs in the process of submucosal invasion and lymph node metastasis in early gastric cancer is still poorly understood. In this study, to address this issue, we collected a total of 59 tumor samples from 27 patients with submucosal-invasive gastric cancers (SMGC), analyzed their genomic profiles by array CGH, and compared them between paired samples of mucosal (MU) and submucosal (SM) invasion (23 pairs), and SM invasion and lymph node (LN) metastasis (9 pairs). Initially, we hypothesized that acquisition of specific CNA(s) is important for these processes. However, we observed no significant difference in the number of genomic CNAs between paired MU and SM, and between paired SM and LN. Furthermore, we were unable to find any CNAs specifically associated with SM invasion or LN metastasis. Among the 23 cases analyzed, 15 had some similar pattern of genomic profiling between SM and MU. Interestingly, 13 of the 15 cases also showed some differences in genomic profiles. These results suggest that the majority of SMGCs are composed of heterogeneous subpopulations derived from the same clonal origin. Comparison of genomic CNAs between SMGCs with and without LN metastasis revealed that gain of 11q13, 11q14, 11q22, 14q32 and amplification of 17q21 were more frequent in metastatic SMGCs, suggesting that these CNAs are related to LN metastasis of early gastric cancer. In conclusion, our data suggest that generation of genetically distinct subclones, rather than acquisition of specific CNA at MU, is integral to the process of submucosal invasion, and that subclones that acquire gain of 11q13, 11q14, 11q22, 14q32 or amplification of 17q21 are likely to become metastatic.
authors.affiliation: Department of Molecular Pathology, Faculty of Medicine, Oita University, Oita, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Kuroda
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Tsukamoto
authors.forename: Lam Tung
authors.initials: LT
authors.lastname: Nguyen
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Noguchi
authors.forename: Ichiro
authors.initials: I
authors.lastname: Takeuchi
authors.forename: Masahiro
authors.initials: M
authors.lastname: Uchida
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Uchida
authors.forename: Naoki
authors.initials: N
authors.lastname: Hijiya
authors.forename: Chisato
authors.initials: C
authors.lastname: Nakada
authors.forename: Tadayoshi
authors.initials: T
authors.lastname: Okimoto
authors.forename: Masaaki
authors.initials: M
authors.lastname: Kodama
authors.forename: Kazunari
authors.initials: K
authors.lastname: Murakami
authors.forename: Keiko
authors.initials: K
authors.lastname: Matsuura
authors.forename: Masao
authors.initials: M
authors.lastname: Seto
authors.forename: Hisao
authors.initials: H
authors.lastname: Ito
authors.forename: Toshio
authors.initials: T
authors.lastname: Fujioka
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Moriyama
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D055028:Comparative Genomic Hybridization / Q000379:methods*; D051356:Cortactin / Q000378:metabolism; D056915:DNA Copy Number Variations / Q000235:genetics; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism / Q000473:pathology*; D018740:Genetic Heterogeneity; D015894:Genome, Human / Q000235:genetics*; D023281:Genomics; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009361:Neoplasm Invasiveness; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D017384:Sequence Deletion / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology*
chemical_list: D051356:Cortactin; D066246:ErbB Receptors; D018719:Erb-b2 Receptor Tyrosine Kinases; C495868:CTTN protein, human; C512478:EGFR protein, human; C508053:ERBB2 protein, human