IDH2 mutations define a unique subtype of breast cancer with altered nuclear polarity Journal Article


Authors: Chiang, S.; Weigelt, B.; Wen, H. C.; Pareja, F.; Raghavendra, A.; Martelotto, L. G.; Burke, K. A.; Basili, T.; Li, A.; Geyer, F. C.; Piscuoglio, S.; Ng, C. K. Y.; Jungbluth, A. A.; Balss, J.; Pusch, S.; Baker, G. M.; Cole, K. S.; Von Deimling, A.; Batten, J. M.; Marotti, J. D.; Soh, H. C.; McCalip, B. L.; Serrano, J.; Lim, R. S.; Siziopikou, K. P.; Lu, S.; Liu, X.; Hammour, T.; Brogi, E.; Snuderl, M.; Iafrate, A. J.; Reis-Filho, J. S.; Schnitt, S. J.
Article Title: IDH2 mutations define a unique subtype of breast cancer with altered nuclear polarity
Abstract: 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 wild-type 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. ©2016 AACR.
Journal Title: Cancer Research
Volume: 76
Issue: 24
ISSN: 0008-5472
Publisher: American Association for Cancer Research  
Date Published: 2016-12-15
Start Page: 7118
End Page: 7129
Language: English
DOI: 10.1158/0008-5472.can-16-0298
PROVIDER: scopus
PUBMED: 27913435
PMCID: PMC5502804
DOI/URL:
Notes: Article -- Export Date: 2 February 2017 -- Source: Scopus
Altmetric Score
MSK Authors
  1. Edi Brogi
    343 Brogi
  2. Achim Jungbluth
    363 Jungbluth
  3. Britta Weigelt
    300 Weigelt
  4. Jorge Sergio Reis
    328 Reis
  5. Kiu Yan Charlotte Ng
    154 Ng
  6. Raymond Sear Lim
    55 Lim
  7. Sarah   Chiang
    51 Chiang
  8. Huei Chi   Wen
    9 Wen
  9. Kathleen   Burke
    55 Burke
  10. Anqi Li
    14 Li