title: Molecular pathogenesis of sporadic colorectal cancers.
abstract: Colorectal cancer (CRC) results from the progressive accumulation of genetic and epigenetic alterations that lead to the transformation of normal colonic mucosa to adenocarcinoma. Approximately 75% of CRCs are sporadic and occur in people without genetic predisposition or family history of CRC. During the past two decades, sporadic CRCs were classified into three major groups according to frequently altered/mutated genes. These genes have been identified by linkage analyses of cancer-prone families and by individual mutation analyses of candidate genes selected on the basis of functional data. In the first half of this review, we describe the genetic pathways of sporadic CRCs and their clinicopathologic features. Recently, large-scale genome analyses have detected many infrequently mutated genes as well as a small number of frequently mutated genes. These infrequently mutated genes are likely described in a limited number of pathways. Gene-oriented models of CRC progression are being replaced by pathway-oriented models. In the second half of this review, we summarize the present knowledge of this research field and discuss its prospects.
authors.affiliation: Department of Diagnostic Pathology, Dokkyo Medical University, 880 Kita-Kobayashi, Mibu, Shimotsuga, Tochigi, 321-0293, Japan. yamagisi@dokkyomed.ac.jp.
authors.forename: Hidetsugu
authors.initials: H
authors.lastname: Yamagishi
authors.affiliation: Department of Pathology, International University of Health and Welfare Hospital, 537-3 Iguchi, Nasushiobara, Tochigi, 329-2763, Japan. hajimek@iuhw.ac.jp.
authors.forename: Hajime
authors.initials: H
authors.lastname: Kuroda
authors.affiliation: Department of Diagnostic Pathology, Dokkyo Medical University, 880 Kita-Kobayashi, Mibu, Shimotsuga, Tochigi, 321-0293, Japan. yimai@s3.dion.ne.jp.|Department of Diagnostic Pathology, Ota Memorial Hospital, Fuji Heavy Industries Health Insurance Society, 455-1 Oshima, Ota, Gunma, 373-8585, Japan. yimai@s3.dion.ne.jp.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Imai
authors.affiliation: Department of Gastroenterology, Dokkyo Medical University, 880 Kita-Kobayashi, Mibu, Shimotsuga, Tochigi, 321-0293, Japan. hiraishi@dokkyomed.ac.jp.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Hiraishi
mesh_terms: D000368:Aged; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology*; D019175:DNA Methylation; D004252:DNA Mutational Analysis / Q000379:methods*; D044127:Epigenesis, Genetic; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D015398:Signal Transduction