TY - JOUR
T1 - The Integrated Genomic Landscape of Thymic Epithelial Tumors
AU - The Cancer Genome Atlas Network
AU - Radovich, Milan
AU - Pickering, Curtis R.
AU - Felau, Ina
AU - Ha, Gavin
AU - Zhang, Hailei
AU - Jo, Heejoon
AU - Hoadley, Katherine A.
AU - Anur, Pavana
AU - Zhang, Jiexin
AU - McLellan, Mike
AU - Bowlby, Reanne
AU - Matthew, Thomas
AU - Danilova, Ludmila
AU - Hegde, Apurva M.
AU - Kim, Jaegil
AU - Leiserson, Mark D.M.
AU - Sethi, Geetika
AU - Lu, Charles
AU - Ryan, Michael
AU - Su, Xiaoping
AU - Cherniack, Andrew D.
AU - Robertson, Gordon
AU - Akbani, Rehan
AU - Spellman, Paul
AU - Weinstein, John N.
AU - Hayes, D. Neil
AU - Raphael, Ben
AU - Lichtenberg, Tara
AU - Leraas, Kristen
AU - Zenklusen, Jean Claude
AU - Ally, Adrian
AU - Appelbaum, Elizabeth L.
AU - Auman, J. Todd
AU - Balasundaram, Miruna
AU - Balu, Saianand
AU - Behera, Madhusmita
AU - Beroukhim, Rameen
AU - Berrios, Mario
AU - Blandino, Giovanni
AU - Bodenheimer, Tom
AU - Bootwalla, Moiz S.
AU - Bowen, Jay
AU - Brooks, Denise
AU - Carcano, Flavio M.
AU - Carlsen, Rebecca
AU - Carvalho, Andre L.
AU - Castro, Patricia
AU - Chalabreysse, Lara
AU - Chin, Lynda
AU - Wilkerson, Matthew D.
N1 - Publisher Copyright:
© 2018 Elsevier Inc.
PY - 2018/2/12
Y1 - 2018/2/12
N2 - Thymic epithelial tumors (TETs) are one of the rarest adult malignancies. Among TETs, thymoma is the most predominant, characterized by a unique association with autoimmune diseases, followed by thymic carcinoma, which is less common but more clinically aggressive. Using multi-platform omics analyses on 117 TETs, we define four subtypes of these tumors defined by genomic hallmarks and an association with survival and World Health Organization histological subtype. We further demonstrate a marked prevalence of a thymoma-specific mutated oncogene, GTF2I, and explore its biological effects on multi-platform analysis. We further observe enrichment of mutations in HRAS, NRAS, and TP53. Last, we identify a molecular link between thymoma and the autoimmune disease myasthenia gravis, characterized by tumoral overexpression of muscle autoantigens, and increased aneuploidy. Radovich et al. perform multi-platform analyses of thymic epithelial tumors. They identify high prevalence of GTF2I mutations and enrichment of mutations in HRAS, NRAS, and TP53 and link overexpression of muscle autoantigens and increased aneuploidy in thymoma and patients’ risk of having myasthenia gravis.
AB - Thymic epithelial tumors (TETs) are one of the rarest adult malignancies. Among TETs, thymoma is the most predominant, characterized by a unique association with autoimmune diseases, followed by thymic carcinoma, which is less common but more clinically aggressive. Using multi-platform omics analyses on 117 TETs, we define four subtypes of these tumors defined by genomic hallmarks and an association with survival and World Health Organization histological subtype. We further demonstrate a marked prevalence of a thymoma-specific mutated oncogene, GTF2I, and explore its biological effects on multi-platform analysis. We further observe enrichment of mutations in HRAS, NRAS, and TP53. Last, we identify a molecular link between thymoma and the autoimmune disease myasthenia gravis, characterized by tumoral overexpression of muscle autoantigens, and increased aneuploidy. Radovich et al. perform multi-platform analyses of thymic epithelial tumors. They identify high prevalence of GTF2I mutations and enrichment of mutations in HRAS, NRAS, and TP53 and link overexpression of muscle autoantigens and increased aneuploidy in thymoma and patients’ risk of having myasthenia gravis.
KW - TCGA
KW - autoimmunity
KW - genomics
KW - myasthenia gravis
KW - proteomics
KW - thymic carcinoma
KW - thymic epithelial tumors
KW - thymoma
KW - transcriptomics
UR - http://www.scopus.com/inward/record.url?scp=85042629007&partnerID=8YFLogxK
U2 - 10.1016/j.ccell.2018.01.003
DO - 10.1016/j.ccell.2018.01.003
M3 - Article
C2 - 29438696
AN - SCOPUS:85042629007
SN - 1535-6108
VL - 33
SP - 244-258.e10
JO - Cancer Cell
JF - Cancer Cell
IS - 2
ER -