title: Differential roles of telomere attrition in type I and II endometrial carcinogenesis.
abstract: Endometrial cancer has been generally categorized into two broad groups of tumors, type I (TI) and type II (TII), with distinct epidemiological/clinical features and genetic alterations. Because telomere attrition appears to trigger genomic instability in certain cancers, we explored the role of telomere dysfunction in endometrial cancer by analyzing telomeres and other markers of telomere status in both tumor types. We describe a new method, telomere chromogenic in situ hybridization, which permitted us to detect cells with short telomeres relative to control (stromal) cells within the same tissue section. Using this method, we found that both types of tumor cells had short telomeres. However, only TII tumors were significantly associated with critical telomere shortening in adjacent, morphologically normal epithelium, suggesting that telomere shortening contributes to the initiation of TII but not TI tumors. To explore this hypothesis, we analyzed mice with critically short telomeres and documented distinctive endometrial lesions that histologically resembled the in situ precursor of TII serous carcinomas; these lesions have not been observed previously in TI mouse models of endometrial cancer. Based on this and previous studies, we propose a model in which telomere attrition contributes to the initiation of TII and progression of TI endometrial cancers.
authors.affiliation: Department of Pathology, UT Southwestern Medical Center, 6000 Harry Hines Blvd., Dallas, TX 75390-9072, USA.
authors.forename: Esra A
authors.initials: EA
authors.lastname: Akbay
authors.forename: Cristina M
authors.initials: CM
authors.lastname: Contreras
authors.forename: Samanthi A
authors.initials: SA
authors.lastname: Perera
authors.forename: James P
authors.initials: JP
authors.lastname: Sullivan
authors.forename: Russell R
authors.initials: RR
authors.lastname: Broaddus
authors.forename: John O
authors.initials: JO
authors.lastname: Schorge
authors.forename: Raheela
authors.initials: R
authors.lastname: Ashfaq
authors.forename: Hossein
authors.initials: H
authors.lastname: Saboorian
authors.forename: Kwok-Kin
authors.initials: KK
authors.lastname: Wong
authors.forename: Diego H
authors.initials: DH
authors.lastname: Castrillon
mesh_terms: D000368:Aged; D000782:Aneuploidy; D000818:Animals; D002471:Cell Transformation, Neoplastic; D016889:Endometrial Neoplasms / Q000473:pathology*; D004717:Endometrium / Q000473:pathology*; D005260:Female; D006801:Humans; D017403:In Situ Hybridization / Q000379:methods; D051379:Mice; D016615:Telomere / Q000502:physiology*