TY - JOUR
T1 - Prevalence of the alternative lengthening of telomeres telomere maintenance mechanism in human cancer subtypes
AU - Heaphy, Christopher M.
AU - Subhawong, Andrea P.
AU - Hong, Seung Mo
AU - Goggins, Michael G.
AU - Montgomery, Elizabeth A.
AU - Gabrielson, Edward
AU - Netto, George J.
AU - Epstein, Jonathan I.
AU - Lotan, Tamara L.
AU - Westra, William H.
AU - Shih, Ie Ming
AU - Iacobuzio-Donahue, Christine A.
AU - Maitra, Anirban
AU - Li, Qing K.
AU - Eberhart, Charles G.
AU - Taube, Janis M.
AU - Rakheja, Dinesh
AU - Kurman, Robert J.
AU - Wu, T. C.
AU - Roden, Richard B.
AU - Argani, Pedram
AU - De Marzo, Angelo M.
AU - Terracciano, Luigi
AU - Torbenson, Michael
AU - Meeker, Alan K.
N1 - Funding Information:
Supported by an NIH postdoctoral training fellowship ( T32 CA067751 ) to C.M.H. and a Department of Defense Breast Cancer Research Program postdoctoral fellowship ( W81XWH-09-1-0650 ) to C.M.H. and by SPORE programs of the National Cancer Institute ( P50 CA88843 , P50 CA58236 , P50 CA62924 , P50 CA058184 , P50 CA098252 ) to Johns Hopkins University School of Medicine.
PY - 2011/10
Y1 - 2011/10
N2 - Approximately 10% to 15% of human cancers lack detectable telomerase activity, and a subset of these maintain telomere lengths by the telomerase-independent telomere maintenance mechanism termed alternative lengthening of telomeres (ALT). The ALT phenotype, relatively common in subtypes of sarcomas and astrocytomas, has rarely been reported in epithelial malignancies. However, the prevalence of ALT has not been thoroughly assessed across all cancer types. We therefore comprehensively surveyed the ALT phenotype in a broad range of human cancers. In total, two independent sets comprising 6110 primary tumors from 94 different cancer subtypes, 541 benign neoplasms, and 264 normal tissue samples were assessed by combined telomere-specific fluorescence in situ hybridization and immunofluorescence labeling for PML protein. Overall, ALT was observed in 3.73% (228/6110) of all tumor specimens, but was not observed in benign neoplasms or normal tissues. This is the first report of ALT in carcinomas arising from the bladder, cervix, endometrium, esophagus, gallbladder, kidney, liver, and lung. Additionally, this is the first report of ALT in medulloblastomas, oligodendrogliomas, meningiomas, schwannomas, and pediatric glioblastoma multiformes. Previous studies have shown associations between ALT status and prognosis in some tumor types; thus, further studies are warranted to assess the potential prognostic significance and unique biology of ALT-positive tumors. These findings may have therapeutic consequences, because ALT-positive cancers are predicted to be resistant to anti-telomerase therapies.
AB - Approximately 10% to 15% of human cancers lack detectable telomerase activity, and a subset of these maintain telomere lengths by the telomerase-independent telomere maintenance mechanism termed alternative lengthening of telomeres (ALT). The ALT phenotype, relatively common in subtypes of sarcomas and astrocytomas, has rarely been reported in epithelial malignancies. However, the prevalence of ALT has not been thoroughly assessed across all cancer types. We therefore comprehensively surveyed the ALT phenotype in a broad range of human cancers. In total, two independent sets comprising 6110 primary tumors from 94 different cancer subtypes, 541 benign neoplasms, and 264 normal tissue samples were assessed by combined telomere-specific fluorescence in situ hybridization and immunofluorescence labeling for PML protein. Overall, ALT was observed in 3.73% (228/6110) of all tumor specimens, but was not observed in benign neoplasms or normal tissues. This is the first report of ALT in carcinomas arising from the bladder, cervix, endometrium, esophagus, gallbladder, kidney, liver, and lung. Additionally, this is the first report of ALT in medulloblastomas, oligodendrogliomas, meningiomas, schwannomas, and pediatric glioblastoma multiformes. Previous studies have shown associations between ALT status and prognosis in some tumor types; thus, further studies are warranted to assess the potential prognostic significance and unique biology of ALT-positive tumors. These findings may have therapeutic consequences, because ALT-positive cancers are predicted to be resistant to anti-telomerase therapies.
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U2 - 10.1016/j.ajpath.2011.06.018
DO - 10.1016/j.ajpath.2011.06.018
M3 - Article
C2 - 21888887
AN - SCOPUS:80053229934
SN - 0002-9440
VL - 179
SP - 1608
EP - 1615
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 4
ER -