TY - JOUR
T1 - Differential roles of telomere attrition in type I and II endometrial carcinogenesis
AU - Akbay, Esra A.
AU - Contreras, Cristina M.
AU - Perera, Samanthi A.
AU - Sullivan, James P.
AU - Broaddus, Russell R.
AU - Schorge, John O.
AU - Ashfaq, Raheela
AU - Saboorian, Hossein
AU - Wong, Kwok Kin
AU - Castrillon, Diego H.
N1 - Funding Information:
Supported by the MD Anderson P50 Uterine Cancer Spore Pilot Project Award (to D.H.C.) and the Sidney Kimmel Translational Science Award (to D.H.C.).
PY - 2008/8
Y1 - 2008/8
N2 - 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.
AB - 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.
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U2 - 10.2353/ajpath.2008.071179
DO - 10.2353/ajpath.2008.071179
M3 - Article
C2 - 18599611
AN - SCOPUS:48749100496
SN - 0002-9440
VL - 173
SP - 536
EP - 544
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 2
ER -