title: Squamous cell carcinomas of the esophagus arise from a telomere-shortened epithelial field.
abstract: Critically shortened telomeres make chromosomes susceptible to the instability and widespread cytogenetic alterations that characterize most human cancers. We hypothesized that the very rapid cell proliferation observed in esophageal squamous cell carcinomas might accelerate telomere shortening and chromosomal instability associated with carcinogenesis. We used a number of telomere measurement techniques including quantitative fluorescence in situ hybridization (Q-FISH) to compare chromosomal aberrations and telomere lengths of individual chromosomes in esophageal squamous cell carcinomas (ESCCs) and nearby non-neoplastic esophageal epithelium (NNEE) cells. Our results showed that the mean telomere length in ESCC cells was significantly less than that in adjacent NNEE cells, and that telomeres in all NNEE cells were significantly shorter than those in normal esophageal epithelium (reported previously). In addition, there was no evidence linking telomere shortening of a particular chromosome to field cancerization in ESCC. However, a mechanistic link between telomere shortening and chromosomal instability was supported by a higher frequency of anaphase/telophase bridges and an increase in the frequency of aneuploidy. This study furthers our understanding of the mechanism by which telomere shortening and chromosomal instability lead to carcinogenesis and field cancerization in the esophagus.
authors.affiliation: Division of Breast and Endocrine Surgery, Department of Surgery, Nihon University School of Medicine, Tokyo 173-8610, Japan. kanmori-dis@umin.ac.jp
authors.forename: Makoto
authors.initials: M
authors.lastname: Kammori
authors.forename: Steven S S
authors.initials: SS
authors.lastname: Poon
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Nakamura
authors.forename: Naotaka
authors.initials: N
authors.lastname: Izumiyama
authors.forename: Naoshi
authors.initials: N
authors.lastname: Ishikawa
authors.forename: Masahiko
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Naomoto
authors.forename: Kaiyo
authors.initials: K
authors.lastname: Takubo
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D043171:Chromosomal Instability; D002869:Chromosome Aberrations; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology; D004947:Esophagus / Q000166:cytology / Q000473:pathology*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D016615:Telomere / Q000378:metabolism / Q000648:ultrastructure; D014407:Tumor Cells, Cultured