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IDH2 Mutations Define a Unique Subtype of Breast Cancer with Altered Nuclear Polarity
Cancer research (Chicago, Ill.), 2016-12, Vol.76 (24), p.7118-7129
Chiang, Sarah
Weigelt, Britta
Wen, Huei-Chi
Pareja, Fresia
Raghavendra, Ashwini
Martelotto, Luciano G
Burke, Kathleen A
Basili, Thais
Li, Anqi
Geyer, Felipe C
Piscuoglio, Salvatore
Ng, Charlotte K Y
Jungbluth, Achim A
Balss, Jörg
Pusch, Stefan
Baker, Gabrielle M
Cole, Kimberly S
von Deimling, Andreas
Batten, Julie M
Marotti, Jonathan D
Soh, Hwei-Choo
McCalip, Benjamin L
Serrano, Jonathan
Lim, Raymond S
Siziopikou, Kalliopi P
Lu, Song
Liu, Xiaolong
Hammour, Tarek
Brogi, Edi
Snuderl, Matija
Iafrate, A John
Reis-Filho, Jorge S
Schnitt, Stuart J
2016
Volltextzugriff (PDF)
Details
Autor(en) / Beteiligte
Chiang, Sarah
Weigelt, Britta
Wen, Huei-Chi
Pareja, Fresia
Raghavendra, Ashwini
Martelotto, Luciano G
Burke, Kathleen A
Basili, Thais
Li, Anqi
Geyer, Felipe C
Piscuoglio, Salvatore
Ng, Charlotte K Y
Jungbluth, Achim A
Balss, Jörg
Pusch, Stefan
Baker, Gabrielle M
Cole, Kimberly S
von Deimling, Andreas
Batten, Julie M
Marotti, Jonathan D
Soh, Hwei-Choo
McCalip, Benjamin L
Serrano, Jonathan
Lim, Raymond S
Siziopikou, Kalliopi P
Lu, Song
Liu, Xiaolong
Hammour, Tarek
Brogi, Edi
Snuderl, Matija
Iafrate, A John
Reis-Filho, Jorge S
Schnitt, Stuart J
Titel
IDH2 Mutations Define a Unique Subtype of Breast Cancer with Altered Nuclear Polarity
Ist Teil von
Cancer research (Chicago, Ill.), 2016-12, Vol.76 (24), p.7118-7129
Ort / Verlag
United States
Erscheinungsjahr
2016
Quelle
MEDLINE
Beschreibungen/Notizen
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. Cancer Res; 76(24); 7118-29. ©2016 AACR.
Sprache
Englisch
Identifikatoren
ISSN: 0008-5472
eISSN: 1538-7445
DOI: 10.1158/0008-5472.CAN-16-0298
Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5502804
Format
–
Schlagworte
Biomarkers, Tumor - genetics
,
Blotting, Western
,
Breast Neoplasms - genetics
,
Breast Neoplasms - pathology
,
Carcinoma, Papillary - genetics
,
Carcinoma, Papillary - pathology
,
Class I Phosphatidylinositol 3-Kinases
,
DNA Mutational Analysis
,
Female
,
High-Throughput Nucleotide Sequencing
,
Humans
,
Immunohistochemistry
,
Isocitrate Dehydrogenase - genetics
,
Phosphatidylinositol 3-Kinases - genetics
,
Polymerase Chain Reaction
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