Prevalence of the Alternative Lengthening of Telomeres Telomere Maintenance Mechanism in Human Cancer Subtypes
Prevalence of the Alternative Lengthening of Telomeres Telomere Maintenance Mechanism in Human Cancer Subtypes
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DOI：
10.1016/j.ajpath.2011.06.018
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发表时间：
2011-10-01
影响因子：
6
通讯作者：
Meeker, Alan K.
中科院分区：
文献类型：
--
作者：
Heaphy, Christopher M.;Subhawong, Andrea P.;Meeker, Alan K.
大约10％至15％的人类癌症缺乏可检测到的端粒酶活性，其中一部分由独立的端粒端粒维持机制维持端粒长度，称为端粒的替代延长（ALT）。在肉瘤和星形胶质细胞瘤的亚型中相对常见的ALT表型在上皮恶性肿瘤中很少报道。但是，在所有癌症类型中尚未彻底评估ALT的患病率。因此，我们在广泛的人类癌症中全面调查了ALT表型。总的来说，通过94种不同的癌症亚型，541种良性肿瘤和264个正常组织样品组成6110个原发性肿瘤的独立组，通过端粒特异性荧光原位杂交和PML蛋白的免疫荧光标记评估了264个正常组织样品。总体而言，在所有肿瘤标本的3.73％（228/6110）中观察到ALT，但在良性肿瘤或正常组织中未观察到ALT。 1608年，这是由膀胱，子宫颈，子宫内膜，食道，胆囊，肾脏，肝脏和肺部引起的癌中ALT的第一份报告。此外，这是髓母细胞瘤，少突endrogliomas，脑膜瘤，schwannomas和小儿胶质母细胞瘤多种形式的第一份报告。先前的研究表明，某些肿瘤类型的ALT状态与预后之间的关联。因此，有必要进行进一步的研究来评估Alt阳性肿瘤的潜在预后意义和独特的生物学。这些发现可能会带来治疗后果，因为预计Alt阳性癌症对抗tel瘤疗法具有抗性。 （Am J Pathol 2011，179：1608-1615; doi：10.1016/j.ajpath.2011.06.018）
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. 1608 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. (Am J Pathol 2011, 179:1608-1615; DOI: 10.1016/j.ajpath.2011.06.018)