Serial genomic analysis of endometrium supports the existence of histologically indistinct endometrial cancer precursors.
Serial genomic analysis of endometrium supports the existence of histologically indistinct endometrial cancer precursors.
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子宫内膜的系列基因组分析支持存在组织学上不明显的子宫内膜癌前体。
DOI：
10.1002/path.5628
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发表时间：
2021-05
期刊：
影响因子：
--
通讯作者：
Castrillon DH
中科院分区：
文献类型：
--
作者：
Aguilar M;Zhang H;Zhang M;Cantarell B;Sahoo SS;Li HD;Cuevas IC;Lea J;Miller DS;Chen H;Zheng W;Gagan J;Lucas E;Castrillon DH
子宫内膜是一个独特的解剖位置，可以反复活检和诊断活检不切除肿瘤病变。我们利用这些特征来回顾性地描述个体女性癌前/癌前连续序列的基因组改变。病例的选择基于(1)子宫内膜癌诊断/子宫切除术和(2)之前的一系列子宫内膜活检，包括一些患者在癌前组织学诊断前的早期活检。为子宫内膜癌基因设计了一个综合小组。对每种癌症进行福尔马林固定、石蜡包埋的标本、之前的活组织检查和匹配的种系样本进行条形码高通量测序，以识别突变并跟踪其起源和等位基因频率进展。总共分析了来自21名患者的92份样本，为早期子宫内膜癌进展提供了新的见解。最终浸润性子宫内膜癌表现出预期的突变谱，在之前的活检中可以检测到典型的驱动突变。值得注意的是，在大多数患者中，在组织病理学诊断为子宫内膜癌前病变之前检测到≥1个癌症突变。在18/21例中，通过异常蛋白水平或免疫组化亚细胞定位证实了≥1个突变，证实了基因组数据，并提供了组织学相关的独特观点。在19例对照子宫内膜中，突变计数较低，缺乏典型的子宫内膜癌热点突变。我们的研究记录了子宫内膜病变的存在，这些病变在组织学上不明确，但却是真正的子宫内膜癌的前兆。©2021作者。《病理学杂志》由John Wiley & Sons， Ltd.代表大不列颠和爱尔兰病理学会出版。
The endometrium is unique as an accessible anatomic location that can be repeatedly biopsied and where diagnostic biopsies do not extirpate neoplastic lesions. We exploited these features to retrospectively characterize serial genomic alterations along the precancer/cancer continuum in individual women. Cases were selected based on (1) endometrial cancer diagnosis/hysterectomy and (2) preceding serial endometrial biopsies including for some patients an early biopsy before a precancer histologic diagnosis. A comprehensive panel was designed for endometrial cancer genes. Formalin‐fixed, paraffin‐embedded specimens for each cancer, preceding biopsies, and matched germline samples were subjected to barcoded high‐throughput sequencing to identify mutations and track their origin and allelic frequency progression. In total, 92 samples from 21 patients were analyzed, providing an opportunity for new insights into early endometrial cancer progression. Definitive invasive endometrial cancers exhibited expected mutational spectra, and canonical driver mutations were detectable in preceding biopsies. Notably, ≥1 cancer mutations were detected prior to the histopathologic diagnosis of an endometrial precancer in the majority of patients. In 18/21 cases, ≥1 mutations were confirmed by abnormal protein levels or subcellular localization by immunohistochemistry, confirming genomic data and providing unique views of histologic correlates. In 19 control endometria, mutation counts were lower, with a lack of canonical endometrial cancer hotspot mutations. Our study documents the existence of endometrial lesions that are histologically indistinct but are bona fide endometrial cancer precursors. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.
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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：
64.8
作者：
通讯作者：
--
影响因子：
50.3
作者：
Berger AC;Korkut A;Kanchi RS;Hegde AM;Lenoir W;Liu W;Liu Y;Fan H;Shen H;Ravikumar V;Rao A;Schultz A;Li X;Sumazin P;Williams C;Mestdagh P;Gunaratne PH;Yau C;Bowlby R;Robertson AG;Tiezzi DG;Wang C;Cherniack AD;Godwin AK;Kuderer NM;Rader JS;Zuna RE;Sood AK;Lazar AJ;Ojesina AI;Adebamowo C;Adebamowo SN;Baggerly KA;Chen TW;Chiu HS;Lefever S;Liu L;MacKenzie K;Orsulic S;Roszik J;Shelley CS;Song Q;Vellano CP;Wentzensen N;Cancer Genome Atlas Research Network;Weinstein JN;Mills GB;Levine DA;Akbani R
通讯作者：
Akbani R
DOI：
10.1056/nejmoa1614814
发表时间：
2017-05-11
期刊：
The New England journal of medicine
影响因子：
--
作者：
Anglesio MS;Papadopoulos N;Ayhan A;Nazeran TM;Noë M;Horlings HM;Lum A;Jones S;Senz J;Seckin T;Ho J;Wu RC;Lac V;Ogawa H;Tessier-Cloutier B;Alhassan R;Wang A;Wang Y;Cohen JD;Wong F;Hasanovic A;Orr N;Zhang M;Popoli M;McMahon W;Wood LD;Mattox A;Allaire C;Segars J;Williams C;Tomasetti C;Boyd N;Kinzler KW;Gilks CB;Diaz L;Wang TL;Vogelstein B;Yong PJ;Huntsman DG;Shih IM
通讯作者：
Shih IM
影响因子：
9.2
作者：
Chang CC;Chow CC;Tellier LC;Vattikuti S;Purcell SM;Lee JJ
通讯作者：
Lee JJ