Genetic events in the progression of adenoid cystic carcinoma of the breast to high-grade triple-negative breast cancer.
Genetic events in the progression of adenoid cystic carcinoma of the breast to high-grade triple-negative breast cancer.
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DOI：
10.1038/modpathol.2016.134
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发表时间：
2016-11
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--
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乳腺腺样囊性癌是一种罕见的三阴性乳腺癌组织学类型，临床表现为惰性，通常由MYB-NFIB融合基因驱动。在这里，我们试图确定与高级别三阴性乳腺癌相关的两个腺样囊性癌的体细胞遗传学改变的剧目。每个病例的不同组分进行拷贝数分析和大规模平行测序，靶向488个基因的所有外显子和选定的调控和内含子区域。采用逆转录PCR和荧光原位杂交技术检测MYB-NFIB易位的存在。MYB-NFIB融合基因在腺样囊性癌及其相关的高级别三阴性乳腺癌组分中均被检测到。虽然这两种情况下的不同组成部分显示了相似的基因拷贝数改变模式，大规模平行测序分析揭示了肿瘤内的遗传异质性。在病例1中，发现从小梁腺样囊性癌进展为高级别三阴性乳腺癌涉及克隆转移，并在高级别三阴性乳腺癌中富集影响EP 300、NOTCH 1、ERBB 2和FGFR 1的突变。在病例2中，克隆KMT 2C突变存在于筛状腺样囊性癌、实体腺样囊性癌和高级别三阴性乳腺癌组分中，而影响MYB的突变仅存在于实体和高级别三阴性乳腺癌区域中，并且靶向STAG 2、KDM 6A和CDK 12的另外三种突变仅限于高级别三阴性乳腺癌。总之，乳腺腺样囊性癌与高级别的转化是由MYB-NFIB融合基因的基础上，类似于其他形式的癌症，可能是由一个马赛克的癌细胞克隆在诊断。从腺样囊性癌进展为无特殊类型的高级别三阴性乳腺癌可能涉及选择肿瘤克隆和/或获得额外的遗传改变。
Adenoid cystic carcinoma of the breast is a rare histologic type of triple-negative breast cancer with an indolent clinical behavior, often driven by the MYB-NFIB fusion gene. Here we sought to define the repertoire of somatic genetic alterations in two adenoid cystic carcinomas associated with high-grade triple-negative breast cancer. The different components of each case were subjected to copy number profiling and massively parallel sequencing targeting all exons and selected regulatory and intronic regions of 488 genes. Reverse transcription PCR and fluorescence in situ hybridization were employed to investigate the presence of the MYB-NFIB translocation. The MYB-NFIB fusion gene was detected in both adenoid cystic carcinomas and their associated high-grade triple-negative breast cancer components. Whilst the distinct components of both cases displayed similar patterns of gene copy number alterations, massively parallel sequencing analysis revealed intra-tumor genetic heterogeneity. In case 1, progression from the trabecular adenoid cystic carcinoma to the high-grade triple-negative breast cancer was found to involve clonal shifts with enrichment of mutations affecting EP300, NOTCH1, ERBB2 and FGFR1 in the high-grade triple-negative breast cancer. In case 2, a clonal KMT2C mutation was present in the cribriform adenoid cystic carcinoma, solid adenoid cystic carcinoma and high-grade triple-negative breast cancer components, whereas a mutation affecting MYB was present only in the solid and high-grade triple-negative breast cancer areas and additional three mutations targeting STAG2, KDM6A and CDK12 were restricted to the high-grade triple-negative breast cancer. In conclusion, adenoid cystic carcinomas of the breast with high-grade transformation are underpinned by MYB-NFIB fusion gene, and, akin to other forms of cancer, may be constituted by a mosaic of cancer cell clones at diagnosis. The progression from adenoid cystic carcinoma to high-grade triple-negative breast cancer of no special type may involve the selection of neoplastic clones and/ or the acquisition of additional genetic alterations.
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DOI：
10.1038/nrc1299
发表时间：
2004-03
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
通讯作者：
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影响因子：
7.3
作者：
Gao J;Aksoy BA;Dogrusoz U;Dresdner G;Gross B;Sumer SO;Sun Y;Jacobsen A;Sinha R;Larsson E;Cerami E;Sander C;Schultz N
通讯作者：
Schultz N
影响因子：
30.8
作者：
Ho, Allen S.;Kannan, Kasthuri;Roy, David M.;Morris, Luc G. T.;Ganly, Ian;Katabi, Nora;Ramaswami, Deepa;Walsh, Logan A.;Eng, Stephanie;Huse, Jason T.;Zhang, Jianan;Dolgalev, Igor;Huberman, Kety;Heguy, Adriana;Viale, Agnes;Drobnjak, Marija;Leversha, Margaret A.;Rice, Christine E.;Singh, Bhuvanesh;Iyer, N. Gopalakrishna;Leemans, C. Rene;Bloemena, Elisabeth;Ferris, Robert L.;Seethala, Raja R.;Gross, Benjamin E.;Liang, Yupu;Sinha, Rileen;Peng, Luke;Raphael, Benjamin J.;Turcan, Sevin;Gong, Yongxing;Schultz, Nikolaus;Kim, Seungwon;Chiosea, Simion;Shah, Jatin P.;Sander, Chris;Lee, William;Chan, Timothy A.
通讯作者：
Chan, Timothy A.
影响因子：
6.4
作者：
Fusco N;Colombo PE;Martelotto LG;De Filippo MR;Piscuoglio S;Ng CK;Lim RS;Jacot W;Vincent-Salomon A;Reis-Filho JS;Weigelt B
通讯作者：
Weigelt B
影响因子：
5
作者：
Costa, Ana F.;Altemani, Albina;Hermsen, Mario
通讯作者：
Hermsen, Mario