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Cancer Diagnostics and Molecular Pathology

BAC Clones Related to Prognosis in Patients with Esophageal Squamous Carcinoma: An Array Comparative Genomic Hybridization Study

^aDepartment of Surgery and Molecular Oncology, Medical Institute of Bioregulation, Kyushu University, Beppu, Japan; ^bDepartment of Surgical Oncology, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan; ^cResearch Institute for Cell Engineering, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Japan; ^dDepartment of Oncological Science (Surgery II), Faculty of Medicine, Oita University, Yufu, Japan

Key Words. Laser microdissection • Genome • Microarray • Clinical samples • Survival curve

Correspondence: Masaki Mori, M.D., Ph.D., F.A.C.S., Department of Surgery and Molecular Oncology, Medical Institute of Bioregulation, Kyushu University, 4546 Tsurumibaru, Beppu 874-0838, Japan. Telephone: 81-977-27-1650; Fax: 81-977-27-1651; e-mail: mmori{at}beppu.kyushu-u.ac.jp or Takashi Hirano, Ph.D., Research Institute for Cell Engineering, National Institute of Advanced Industrial Science and Technology (AIST), 1-1-1 Higashi, Tsukuba, Ibaraki 305-8566, Japan. Telephone: 81-29-861-6152; Fax: 81-29-861-6144; e-mail: hirano-takashi{at}aist.go.jp

Purpose. The prognosis of patients with esophageal carcinoma is poor. To identify genomic alterations associated with poor patient prognosis, we analyzed whole DNA copy number profiles of esophageal squamous carcinomas (ESCs) using array-based comparative genomic hybridization (aCGH).

Materials and Methods. Twenty-one operated and two biopsied cases of esophageal squamous cancer were examined for study. Each sample was laser microdissected to obtain pure cancer cell populations. The extracted DNA was analyzed using aCGH.

Results. One of the most representative alterations was a previously reported amplification at 11q13.3. In addition, some novel alterations, such as deletion of 16p13.3, were identified. Of the 19 patients who were reassessed more than 5 years after the operation, nine were still living and 10 had died from disease recurrence. When aCGH profiles from the surviving group and the deceased group were compared, significant differences were recognized in 68 of 4,030 bacterial artificial chromosome (BAC) clones. Almost half of these clones were present at nine limiting regions in 4q, 13q, 20q, and Xq. For 22 of these 68 BAC clones, there also was a significant difference in the Kaplan-Meier survival curve, using the log-rank test, when comparing patients who had an alteration in a particular clone with those who did not.

Conclusions. aCGH study of esophageal squamous cancer clearly identified BAC clones that are related to the prognosis of patients. These clones give us the opportunity to determine specific genes that are associated with cancer progression.

Disclosure of potential conflicts of interest is found at the end of this article.

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