Whole-Exome Sequencing of Rare Site Endometriosis-Associated Cancer.
Whole-Exome Sequencing of Rare Site Endometriosis-Associated Cancer.
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DOI：
10.3390/diseases9010014
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发表时间：
2021-02-04
期刊：
影响因子：
--
通讯作者：
Kyo S
中科院分区：
文献类型：
--
作者：
Kurose S;Nakayama K;Razia S;Ishikawa M;Ishibashi T;Yamashita H;Sato S;Sakiyama A;Yoshioka S;Kobayashi M;Nakayama S;Otuski Y;Ishikawa N;Kyo S
卵巢外子宫内膜异位症恶变少见，其发生机制尚不清楚。为了阐明罕见位点乳腺癌相关癌症（RSEAC）的可行变体，我们对两名患者的肿瘤进行了全外显子组测序。在这两种情况下，肠道受到影响，虽然组织学是透明细胞癌和未分化癌，分别。因此，这些病例被称为胰腺炎相关性肠道肿瘤（EIAT）。在肿瘤抑制基因ARID 1A、PTEN和p53中鉴定出可操作的变体（所有移码突变）;然而，未鉴定出致癌变体。两例病例均为微卫星稳定。未分化癌患者表现出高变基因和同源重组缺陷表型。在患者1中，显性突变特征是特征30（乳腺癌的小子集）和19（毛细胞性星形细胞瘤），在患者2中，显性突变特征是特征5（乳腺癌的小子集）和3（乳腺癌、卵巢癌和胰腺癌）。免疫组化显示两例患者均呈CD 8和PD-1阳性表达;患者1也显示PDL-1阳性表达。我们的研究结果表明，RSEAC与肿瘤抑制基因的变异作为表观遗传学改变。基于突变特征的全外显子组测序可能有助于选择辅助化疗方案。RSEAC中的高CD 8和PD-1表达表明免疫检查点抑制剂可用于治疗。
Malignant transformation of extraovarian endometriosis is rare, with the carcinogenesis mechanism unclear. To clarify the actionable variants of rare-site endometriosis-associated cancer (RSEAC), we performed whole-exome sequencing for the tumor, in two patients. The intestine was affected in both cases, although the histology was that of clear cell carcinoma and undifferentiated carcinoma, respectively. Therefore, the cases were referred to as endometriosis-associated intestinal tumors (EIATs). Actionable variants (all frameshift mutations) were identified in tumor suppressor genes ARID1A, PTEN, and p53; however, no oncogenic variants were identified. Both cases were microsatellite stable. The patient with undifferentiated carcinoma exhibited hypermutator and homologous recombination deficiency phenotypes. The dominant mutation signatures were signature 30 (small subset of breast cancers) and 19 (pilocytic astrocytoma) in patient 1, and signature 5 (small subset of breast cancers) and 3 (breast, ovarian, and pancreatic cancers) in patient 2. Immunohistochemistry revealed positive CD8 and PD-1 expression in both patients; patient 1 also showed positive PDL-1 expression. Our results suggest that RSEAC is associated with variants of tumor suppressor genes as epigenetic alterations. Mutation signature-based whole-exome sequencing could be useful to select an adjuvant chemotherapy regimen. High CD8 and PD-1 expression in RSEAC suggests that immune checkpoint inhibitors are useful for treatment.
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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：
5.8
作者：
JUDD, HL;JUDD, GE;YEN, SSC
通讯作者：
YEN, SSC
影响因子：
64.8
作者：
Moore, Luiza;Leongamornlert, Daniel;Stratton, Michael R.
通讯作者：
Stratton, Michael R.
DOI：
10.1016/s0002-9378(97)70550-7
发表时间：
1997-03-01
影响因子：
9.8
作者：
Brinton, LA;Gridley, G;Bergqvist, A
通讯作者：
Bergqvist, A
影响因子：
--
作者：
Ishikawa M;Nakayama K;Nakamura K;Ono R;Sanuki K;Yamashita H;Ishibashi T;Minamoto T;Iida K;Razia S;Ishikawa N;Kyo S
通讯作者：
Kyo S