Gradual telomere shortening and increasing chromosomal instability among PanIN grades and normal ductal epithelia with and without cancer in the pancreas.
Gradual telomere shortening and increasing chromosomal instability among PanIN grades and normal ductal epithelia with and without cancer in the pancreas.
复制标题
在患有或不患有胰腺癌的 PanIN 等级和正常导管上皮中，端粒逐渐缩短并增加染色体不稳定性。
DOI：
10.1371/journal.pone.0117575
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Arai T
中科院分区：
文献类型：
--
作者：
Matsuda Y;Ishiwata T;Izumiyama-Shimomura N;Hamayasu H;Fujiwara M;Tomita K;Hiraishi N;Nakamura K;Ishikawa N;Aida J;Takubo K;Arai T
大量的证据支持端粒功能障碍在癌症发生中的关键作用，由于诱导染色体不稳定性。为了研究胰腺癌前病变中的端粒缩短，我们使用定量荧光原位杂交测量了正常胰腺导管上皮、胰腺上皮内瘤变（PanIN）和癌症中的端粒长度。所采用的材料包括手术切除的胰腺标本无癌（n = 33）和浸润性导管癌（n = 36），以及对照尸检病例（n = 150）。与正常导管相比，PanIN-1，-2和-3和癌症中的端粒长度减少。此外，癌症中的端粒比PanIN-1和PanIN-2短。端粒长度与组织学类型、病变部位或癌症分期无关。有或没有癌症的PanIN显示出相似的端粒长度。不典型有丝分裂和后期桥的发生率与端粒长度呈负相关，它们是染色体不稳定的形态学特征。正常导管上皮的端粒随着年龄的增长而变短，PanIN或癌症中的端粒比年龄匹配的对照组短，这表明即使没有组织学变化，端粒也会缩短。我们的数据有力地表明，端粒缩短发生在胰腺癌的早期阶段，并与癌前发展的进展。胰腺导管上皮细胞端粒缩短和染色体不稳定可能与胰腺癌的发生有关。胰腺导管病变中端粒长度的测定可能对胰腺癌的准确检测和风险评估有价值。
A large body of evidence supports a key role for telomere dysfunction in carcinogenesis due to the induction of chromosomal instability. To study telomere shortening in precancerous pancreatic lesions, we measured telomere lengths using quantitative fluorescence in situ hybridization in the normal pancreatic duct epithelium, pancreatic intraepithelial neoplasias (PanINs), and cancers. The materials employed included surgically resected pancreatic specimens without cancer (n = 33) and with invasive ductal carcinoma (n = 36), as well as control autopsy cases (n = 150). In comparison with normal ducts, telomere length was decreased in PanIN-1, −2 and −3 and cancer. Furthermore, telomeres were shorter in cancer than in PanIN-1 and −2. Telomere length in cancer was not associated with histological type, lesion location, or cancer stage. PanINs with or without cancer showed similar telomere lengths. The incidences of atypical mitosis and anaphase bridges, which are morphological characteristics of chromosomal instability, were negatively correlated with telomere length. The telomeres in normal duct epithelium became shorter with aging, and those in PanINs or cancers were shorter than in age-matched controls, suggesting that telomere shortening occurs even when histological changes are absent. Our data strongly suggest that telomere shortening occurs in the early stages of pancreatic carcinogenesis and progresses with precancerous development. Telomere shortening and chromosomal instability in the duct epithelium might be associated with carcinogenesis of the pancreas. Determination of telomere length in pancreatic ductal lesions may be valuable for accurate detection and risk assessment of pancreatic cancer.
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DOI：
10.1038/modpathol.2009.114
发表时间：
2009-11
期刊：
Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc
影响因子：
--
作者：
通讯作者：
--
影响因子：
2.9
作者：
Baumgart, Mario;Werther, Meike;Heinmoeller, Ernst
通讯作者：
Heinmoeller, Ernst
影响因子：
3.8
作者：
Bidoli E;Fratino L;Bruzzone S;Pappagallo M;De Paoli P;Tirelli U;Serraino D
通讯作者：
Serraino D
影响因子：
3.3
作者：
Aida, Junko;Izumiyama-Shimomura, Naotaka;Takubo, Kaiyo
通讯作者：
Takubo, Kaiyo
影响因子：
1.2
作者：
Amosenko, F. A.;Kazubskaya, T. P.;Kalinin, V. N.
通讯作者：
Kalinin, V. N.