Clonal relationships between lobular carcinoma in situ and other breast malignancies.
Clonal relationships between lobular carcinoma in situ and other breast malignancies.
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DOI：
10.1186/s13058-016-0727-z
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发表时间：
2016-06-23
期刊：
影响因子：
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通讯作者：
King TA
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文献类型：
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作者：
Begg CB;Ostrovnaya I;Carniello JV;Sakr RA;Giri D;Towers R;Schizas M;De Brot M;Andrade VP;Mauguen A;Seshan VE;King TA
最近的证据表明，小叶原位癌（LCIS）可以是导管和小叶表型浸润性乳腺癌的克隆前体。我们试图通过对接受乳房切除术的女性新鲜冷冻乳房标本的广泛研究来证实这些发现。前瞻性地确定有LCIS病史的患者进行治疗性乳房切除术。收集冷冻组织块，筛选感兴趣的病变，并进行显微切割和DNA提取。进行拷贝数分析、全外显子组测序或两者。克隆相关性进行了评估，使用专门的统计技术，为此目的而开发。排除基因分型失败后，成功评价了30例患者的84处病变。强有力的证据表明，LCIS病变和浸润性癌之间存在克隆相关性，小叶癌病例占优势。解剖学上不同的原位病变的导管和小叶组织学也被证明是经常克隆相关。这些来自患有LCIS伴或不伴浸润性癌的女性的数据证实LCIS通常是浸润性小叶癌的克隆前体，并且LCIS的不同病灶经常共享克隆起源，LCIS和导管原位癌的病灶也是如此。本文的在线版本（doi：10.1186/s13058-016-0727-z）包含补充材料，可供授权用户使用。
Recent evidence suggests that lobular carcinoma in situ (LCIS) can be a clonal precursor of invasive breast cancers of both the ductal and lobular phenotypes. We sought to confirm these findings with an extensive study of fresh frozen breast specimens from women undergoing mastectomy. Patients with a history of LCIS presenting for therapeutic mastectomy were identified prospectively. Frozen tissue blocks were collected, screened for lesions of interest, and subjected to microdissection and DNA extraction. Copy number profiling, whole-exome sequencing, or both were performed. Clonal relatedness was assessed using specialized statistical techniques developed for this purpose. After exclusions for genotyping failure, a total of 84 lesions from 30 patients were evaluated successfully. Strong evidence of clonal relatedness was observed between an LCIS lesion and the invasive cancer for the preponderance of cases with lobular carcinoma. Anatomically distinct in situ lesions of both ductal and lobular histology were also shown to be frequently clonally related. These data derived from women with LCIS with or without invasive cancer confirm that LCIS is commonly the clonal precursor of invasive lobular carcinoma and that distinct foci of LCIS frequently share a clonal origin, as do foci of LCIS and ductal carcinoma in situ. The online version of this article (doi:10.1186/s13058-016-0727-z) contains supplementary material, which is available to authorized users.