Telomere shortening occurs in subsets of normal breast epithelium as well as in situ and invasive carcinoma
Telomere shortening occurs in subsets of normal breast epithelium as well as in situ and invasive carcinoma
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DOI：
10.1016/s0002-9440(10)63180-x
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发表时间：
2004-03-01
影响因子：
6
通讯作者：
Argani, P
中科院分区：
文献类型：
--
作者：
Meeker, AK;Hicks, JL;Argani, P
在设置失活的DNA损伤敏感的检查点，严重缩短端粒促进染色体不稳定性和广泛的细胞遗传学改变的类型，大多数人类癌症的特征。使用直接端粒荧光原位杂交技术，我们分析了114例浸润性乳腺癌，29例原位癌病变，10例良性增生性病变，以及男性和女性乳腺不同的正常上皮成分。我们发现，在大多数（52.5%）的浸润性癌显著端粒缩短;较小的浸润性癌的子集表现出中度端粒缩短（17.5%）或正常端粒长度（21%），而一个小的亚组（5%）含有延长的端粒。引人注目的是，大多数（78%）导管原位癌表现出显着或中度缩短端粒。令人惊讶的是，与迄今为止研究的所有其他正常上皮细胞不同，在大约50%的组织学正常的终末导管小叶单位（大多数乳腺癌被认为是由此产生的）中的良性分泌细胞中观察到中度端粒缩短，而在女性乳腺或男性乳腺导管的肌上皮细胞或正常的大泌乳导管（乳腺癌很少发生）中没有观察到这种缩短。我们推测，这种缩短的结果，尿道驱动，生理性增殖，并可能描绘一个人口的上皮细胞在随后的恶性转化的风险。
In the setting of inactivated DNA damage-sensitive checkpoints, critically shortened telomeres promote chromosomal instability and the types of widespread cytogenetic alterations that characterize most human carcinomas. Using a direct telomere fluorescence in situ hybridization technique, we analyzed 114 invasive breast carcinomas, 29 carcinoma in situ lesions, 10 benign proliferative lesions, and different normal epithelial components of the male and female breast. We found marked telomere shortening in the majority (52.5%) of invasive carcinomas; smaller subsets of invasive carcinoma demonstrated moderate telomere shortening (17.5%) or normal telomere lengths (21%), while a small subgroup (5%) contained elongated telomeres. Strikingly, the majority (78%) of ductal carcinoma in situ demonstrated markedly or moderately shortened telomeres. Surprisingly, unlike all other normal epithelia studied to date, moderate telomere shortening was observed in benign secretory cells in approximately 50% of histologically-normal terminal duct lobular units (from which most breast cancer is thought to arise), while such shortening was not seen in myoepithelial cells or normal large lactiferous ducts of the female breast or male breast ducts (from which breast cancer infrequently arises). We postulate that such shortening is the result of hormonally driven, physiological proliferation, and may delineate a population of epithelial cells at risk for subsequent malignant transformation.