IDH2 Mutations Define a Unique Subtype of Breast Cancer with Altered Nuclear Polarity

被引：97

作者：

Chiang, Sarah ^{[1
]}

Weigelt, Britta ^{[1
]}

Wen, Huei-Chi ^{[1
,18
]}

Pareja, Fresia ^{[1
]}

Raghavendra, Ashwini ^{[1
]}

Martelotto, Luciano G. ^{[1
]}

Burke, Kathleen A. ^{[1
]}

Basili, Thais ^{[1
]}

Li, Anqi ^{[1
]}

Geyer, Felipe C. ^{[1
]}

Piscuoglio, Salvatore ^{[1
]}

Ng, Charlotte K. Y. ^{[1
]}

Jungbluth, Achim A. ^{[1
]}

Balss, Joerg ^{[2
]}

Pusch, Stefan ^{[2
]}

Baker, Gabrielle M. ^{[3
]}

Cole, Kimberly S. ^{[4
]}

von Deimling, Andreas ^{[2
,5
]}

Batten, Julie M. ^{[6
]}

Marotti, Jonathan D. ^{[7
]}

Soh, Hwei-Choo ^{[8
]}

McCalip, Benjamin L. ^{[9
]}

Serrano, Jonathan ^{[10
,11
]}

Lim, Raymond S. ^{[1
]}

Siziopikou, Kalliopi P. ^{[12
]}

Lu, Song ^{[13
]}

Liu, Xiaolong ^{[14
]}

Hammour, Tarek ^{[15
]}

Brogi, Edi ^{[1
]}

Snuderl, Matija ^{[10
,11
]}

Iafrate, A. John ^{[16
]}

Reis-Filho, Jorge S. ^{[1
]}

Schnitt, Stuart J. ^{[16
,17
]}

机构：

[1] Mem Sloan Kettering Canc Ctr, Dept Pathol, 1275 York Ave, New York, NY 10021 USA

[2] German Canc Res Ctr, Clin Cooperat Unit Neuropathol, German Consortium Translat Canc Res DKTK, Heidelberg, Germany

[3] Univ Chicago, Dept Pathol, 5841 S Maryland Ave, Chicago, IL 60637 USA

[4] Univ Iowa Hosp & Clin, Dept Pathol, Iowa City, IA 52242 USA

[5] Heidelberg Univ, Inst Pathol, Dept Neuropathol, Heidelberg, Germany

[6] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA

[7] Dartmouth Hitchcock Med Ctr, Dept Pathol, Lebanon, NH 03766 USA

[8] North Shore Private Hosp, Pathol North, St Leonards, NSW, Australia

[9] Miami Valley Hosp, Dayton, OH USA

[10] NYU, Dept Pathol, Langone Med Ctr, 550 1St Ave, New York, NY 10016 USA

[11] Sch Med, New York, NY USA

[12] Northwestern Univ, Dept Pathol, Feinberg Sch Med, Chicago, IL 60611 USA

[13] Mon Gen Hosp, Dept Pathol, Morgantown, WV USA

[14] ABQ Hlth Partners, Albuquerque, NM USA

[15] Maine Med Ctr, Portland, ME 04102 USA

[16] Harvard Med Sch, Dept Pathol, Boston, MA USA

[17] Beth Israel Deaconess Med Ctr, Dept Pathol, 330 Brookline Ave, Boston, MA 02215 USA

[18] Icahn Sch Med Mt Sinai, Dept Dermatol, New York, NY 10029 USA

来源：

CANCER RESEARCH | 2016年 / 76卷 / 24期

关键词：

PAPILLARY THYROID-CARCINOMA; HER2 GENE AMPLIFICATION; TALL CELL VARIANT; 2-HYDROXYGLUTARATE; HYPERMETHYLATION; DIFFERENTIATION; ADENOCARCINOMA; PROGRESSION; PHENOTYPE; CULTURES;

D O I：

10.1158/0008-5472.CAN-16-0298

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Solid papillary carcinoma with reverse polarity (SPCRP) is a rare breast cancer subtype with an obscure etiology. In this study, we sought to describe its unique histopathologic features and to identify the genetic alterations that underpin SPCRP using massively parallel whole-exome and targeted sequencing. The morphologic and immunohistochemical features of SPCRP support the invasive nature of this subtype. Ten of 13 (77%) SPCRPs harbored hotspot mutations at R172 of the isocitrate dehydrogenase IDH2, of which 8 of 10 displayed concurrent pathogenic mutations affecting PIK3CA or PIK3R1. One of the IDH2 wildtype SPCRPs harbored a TET2 Q548* truncating mutation coupled with a PIK3CA H1047R hotspot mutation. Functional studies demonstrated that IDH2 and PIK3CA hotspot mutations are likely drivers of SPCRP, resulting in its reversed nuclear polarization phenotype. Our results offer a molecular definition of SPCRP as a distinct breast cancer subtype. Concurrent IDH2 and PIK3CA mutations may help diagnose SPCRP and possibly direct effective treatment. (C)2016 AACR.

引用

页码：7118 / 7129

页数：12

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