Breast carcinoma and Lynch syndrome: molecular analysis of tumors arising in mutation carriers, non-carriers, and sporadic cases.
Breast carcinoma and Lynch syndrome: molecular analysis of tumors arising in mutation carriers, non-carriers, and sporadic cases.
复制标题
DOI：
10.1186/bcr3205
复制
发表时间：
2012-06-12
期刊：
影响因子：
--
通讯作者：
Peltomäki P
中科院分区：
文献类型：
--
作者：
Lotsari JE;Gylling A;Abdel-Rahman WM;Nieminen TT;Aittomäki K;Friman M;Pitkänen R;Aarnio M;Järvinen HJ;Mecklin JP;Kuopio T;Peltomäki P
乳腺癌是女性最常见的癌症，但在Lynch综合征(LS)中其发病率并未增加，关于LS相关乳腺癌中DNA错配修复缺陷(MMR)的研究得出了相互矛盾的结果。本研究旨在解决乳腺癌是否属于LS肿瘤谱的问题。从全国登记的200个LS家系中确定了所有可用的乳腺癌的MMR状态和表观遗传学特征(23个肿瘤来自突变携带者，18个来自非携带者)。以MMR基因突变携带者中的散发性乳腺癌(n=49)和其他癌症(n=105)为对照。突变携带者乳腺癌中MMR缺失、微卫星不稳定或两者兼有的乳腺癌比例(13/20，65%)显著高于非突变携带者(0/14，0%)(P=0.00016)。乳腺癌诊断的平均年龄在携带者(56岁)和非携带者(54岁)中相似，但在突变携带者中，MMR缺陷肿瘤的平均诊断年龄低于熟练肿瘤(53岁对61岁，P=0.027)。在突变携带者中，乳腺癌中缺失MMR蛋白的频率(65%)低于所研究的其他七种肿瘤类型中的任何一种(75%至100%)。肿瘤抑制基因启动子甲基化模式是器官特异性的，突变携带者和非携带者的乳腺癌之间相似。MMR基因突变携带者的乳腺癌在许多方面(例如，一般的临床病理和表观遗传学特征)与普通乳腺癌相似。MMR状态有一个区别：超过一半的人是典型的LS光谱肿瘤的MMR缺陷，而其余的MMR熟练的亚群可能发展不同。这一结果对突变携带者的适当监测具有重要意义，并可能与特定病例的LS诊断相关。
Breast carcinoma is the most common cancer in women, but its incidence is not increased in Lynch syndrome (LS) and studies on DNA mismatch repair deficiency (MMR) in LS-associated breast cancers have arrived at conflicting results. This study aimed to settle the question as to whether breast carcinoma belongs to the LS tumor spectrum. MMR status and epigenetic profiles were determined for all available breast carcinomas identified among 200 LS families from a nation-wide registry (23 tumors from mutation carriers and 18 from non-carriers). Sporadic breast carcinomas (n = 49) and other cancers (n = 105) from MMR gene mutation carriers were studied for comparison. The proportion of breast carcinomas that were MMR-deficient based on absent MMR protein, presence of microsatellite instability, or both was significantly (P = 0.00016) higher among breast carcinomas from mutation carriers (13/20, 65%) compared to non-carriers (0/14, 0%). While the average age at breast carcinoma diagnosis was similar in carriers (56 years) and non-carriers (54 years), it was lower for MMR-deficient versus proficient tumors in mutation carriers (53 years versus 61 years, P = 0.027). Among mutation carriers, absent MMR protein was less frequent in breast carcinoma (65%) than in any of seven other tumor types studied (75% to 100%). Tumor suppressor promoter methylation patterns were organ-specific and similar between breast carcinomas from mutation carriers and non-carriers. Breast carcinoma from MMR gene mutation carriers resembles common breast carcinoma in many respects (for example, general clinicopathological and epigenetic profiles). MMR status makes a distinction: over half are MMR-deficient typical of LS spectrum tumors, while the remaining subset which is MMR-proficient may develop differently. The results are important for appropriate surveillance in mutation carriers and may be relevant for LS diagnosis in selected cases.
登录
查看更多内容
影响因子：
2.4
作者：
Buyru, Nur;Altinisik, Julide;Dalay, Nejat
通讯作者：
Dalay, Nejat
影响因子：
3.8
作者：
Jensen, Uffe Birk;Sunde, Lone;Nilbert, Mef
通讯作者：
Nilbert, Mef
影响因子：
82.9
作者：
NYSTROMLAHTI, M;KRISTO, P;PELTOMAKI, P
通讯作者：
PELTOMAKI, P
影响因子：
6.4
作者：
Aktan-Collan, K;Haukkala, A;Kääriäinen, H
通讯作者：
Kääriäinen, H
影响因子：
14.9
作者：
Nygren AO;Ameziane N;Duarte HM;Vijzelaar RN;Waisfisz Q;Hess CJ;Schouten JP;Errami A
通讯作者：
Errami A