title: Impact of chromosome 17q deletion in the primary lesion of colorectal cancer on liver metastasis.
abstract: Colorectal cancer is a prevalent malignancy worldwide, and investigations are required to elucidate the underlying carcinogenic mechanisms. Amongst these mechanisms,de novocarcinogenesis and the adenoma to carcinoma sequence, are the most understood. Metastasis of colorectal cancer to the liver often results in fatality, therefore, it is important for any associated risk factors to be identified. Regarding the treatment of the disease, it is important to manage not only the primary colorectal tumor, but also the liver metastases. Previously, through gene variation analysis, chromosomal loss has been indicated to serve an important role in liver metastasis. Such analysis may aid in the prediction of liver metastasis risk, alongside individual responses to treatment, thus improving the management of colorectal cancer. In the present study, we aimed to clarify a cause of the liver metastasis of colorectal cancer using comparative genomic hybridization analysis. A total of 116 frozen samples were analyzed from patients with advanced colorectal cancer that underwent surgery from 2004 to 2011. The present study analyzed mutations within tumor suppressor genes non-metastatic gene 23 (NM23), deleted in colorectal carcinoma (DCC) and deleted in pancreatic carcinoma, locus 4 (DPC4), which are located on chromosomes 17 and 18 and have all been reported to affect liver metastasis of colorectal cancer. The association between chromosomal abnormalities (duplication and deletion) and liver metastasis of colorectal cancer was evaluated using comparative genomic hybridization. Cluster analysis indicated that the group of patients lacking the long arm of chromosome 17 demonstrated the highest rate of liver metastasis. No significant association was observed between the frequency of liver metastases for synchronous and heterochronous colorectal cancer cases and gene variation (P=0.206). However, when these liver metastasis cases were divided into the synchronous and heterochronous types, the ratio of each was significantly different between gene variation groups, classified by the existence of the 17q deletion (P=0.023). These results indicate that the deletion of 17q may act as a predictive marker of liver metastasis in postoperative states.
authors.affiliation: Department of Coloproctological Surgery, Faculty of Medicine, Juntendo University School of Medicine, Tokyo 113-8421, Japan.
authors.forename: Masaya
authors.initials: M
authors.lastname: Kawai
authors.affiliation: Department of Coloproctological Surgery, Faculty of Medicine, Juntendo University School of Medicine, Tokyo 113-8421, Japan.
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Komiyama
authors.affiliation: Department of Coloproctological Surgery, Faculty of Medicine, Juntendo University School of Medicine, Tokyo 113-8421, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Hosoya
authors.affiliation: Department of Coloproctological Surgery, Faculty of Medicine, Juntendo University School of Medicine, Tokyo 113-8421, Japan.
authors.forename: Haruna
authors.initials: H
authors.lastname: Okubo
authors.affiliation: Department of Coloproctological Surgery, Faculty of Medicine, Juntendo University School of Medicine, Tokyo 113-8421, Japan.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Fujii
authors.affiliation: Department of Coloproctological Surgery, Faculty of Medicine, Juntendo University School of Medicine, Tokyo 113-8421, Japan.
authors.forename: Norihiko
authors.initials: N
authors.lastname: Yokoyama
authors.affiliation: Department of Coloproctological Surgery, Faculty of Medicine, Juntendo University School of Medicine, Tokyo 113-8421, Japan.
authors.forename: Chiyo
authors.initials: C
authors.lastname: Sato
authors.affiliation: Department of Coloproctological Surgery, Faculty of Medicine, Juntendo University School of Medicine, Tokyo 113-8421, Japan.
authors.forename: Takae
authors.initials: T
authors.lastname: Ueyama
authors.affiliation: Department of Coloproctological Surgery, Faculty of Medicine, Juntendo University School of Medicine, Tokyo 113-8421, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Okuzawa
authors.affiliation: Department of Coloproctological Surgery, Faculty of Medicine, Juntendo University School of Medicine, Tokyo 113-8421, Japan.
authors.forename: Michitoshi
authors.initials: M
authors.lastname: Goto
authors.affiliation: Department of Coloproctological Surgery, Faculty of Medicine, Juntendo University School of Medicine, Tokyo 113-8421, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kojima
authors.affiliation: Department of Coloproctological Surgery, Faculty of Medicine, Juntendo University School of Medicine, Tokyo 113-8421, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Takahashi
authors.affiliation: Department of Coloproctological Surgery, Faculty of Medicine, Juntendo University School of Medicine, Tokyo 113-8421, Japan.
authors.forename: Kiichi
authors.initials: K
authors.lastname: Sugimoto
authors.affiliation: Department of Coloproctological Surgery, Faculty of Medicine, Juntendo University School of Medicine, Tokyo 113-8421, Japan.
authors.forename: Shun
authors.initials: S
authors.lastname: Ishiyama
authors.affiliation: Department of Coloproctological Surgery, Faculty of Medicine, Juntendo University School of Medicine, Tokyo 113-8421, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Munakata
authors.affiliation: Link Genomics Inc., Tokyo 103-0012, Japan.
authors.forename: Dai
authors.initials: D
authors.lastname: Ogura
authors.affiliation: Link Genomics Inc., Tokyo 103-0012, Japan.
authors.forename: Shin-Ichiro
authors.initials: SI
authors.lastname: Niwa
authors.affiliation: Department of Coloproctological Surgery, Faculty of Medicine, Juntendo University School of Medicine, Tokyo 113-8421, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Tomiki
authors.affiliation: Department of Coloproctological Surgery, Faculty of Medicine, Juntendo University School of Medicine, Tokyo 113-8421, Japan.
authors.forename: Takumi
authors.initials: T
authors.lastname: Ochiai
authors.affiliation: Department of Coloproctological Surgery, Faculty of Medicine, Juntendo University School of Medicine, Tokyo 113-8421, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Sakamoto
keywords: chromosome 17; cluster analysis; colorectal cancer; comparative genomic hybridization; liver metastasis