TY - JOUR
T1 - SMARCA4 inactivation defines a group of undifferentiated thoracic malignancies transcriptionally related to BAF-deficient sarcomas
AU - Le Loarer, Francois
AU - Watson, Sarah
AU - Pierron, Gaelle
AU - De Montpreville, Vincent Thomas
AU - Ballet, Stelly
AU - Firmin, Nelly
AU - Auguste, Aurelie
AU - Pissaloux, Daniel
AU - Boyault, Sandrine
AU - Paindavoine, Sandrine
AU - Dechelotte, Pierre Joseph
AU - Besse, Benjamin
AU - Vignaud, Jean Michel
AU - Brevet, Marie
AU - Fadel, Elie
AU - Richer, Wilfrid
AU - Treilleux, Isabelle
AU - Masliah-Planchon, Julien
AU - Devouassoux-Shisheboran, Mojgan
AU - Zalcman, Gerard
AU - Allory, Yves
AU - Bourdeaut, Franck
AU - Thivolet-Bejui, Francoise
AU - Ranchere-Vince, Dominique
AU - Girard, Nicolas
AU - Lantuejoul, Sylvie
AU - Galateau-Sallé, Francoise
AU - Coindre, Jean Michel
AU - Leary, Alexandra
AU - Delattre, Olivier
AU - Blay, Jean Yves
AU - Tirode, Franck
N1 - Publisher Copyright:
© 2015 Nature America, Inc.
PY - 2015/9/29
Y1 - 2015/9/29
N2 - While investigating cohorts of unclassified sarcomas by RNA sequencing, we identified 19 cases with inactivation of SMARCA4, which encodes an ATPase subunit of BAF chromatin-remodeling complexes. Clinically, the cases were all strikingly similar, presenting as compressive mediastino-pulmonary masses in 30- to 35-year-old adults with a median survival time of 7 months. To help define the nosological relationships of these tumors, we compared their transcriptomic profiles with those of SMARCA4-mutated small-cell carcinomas of the ovary, hypercalcemic type (SCCOHTs), SMARCB1-inactivated malignant rhabdoid tumors (MRTs) and lung carcinomas (of which 10% display SMARCA4 mutations). Gene profiling analyses demonstrated that these tumors were distinct from lung carcinomas but related to MRTs and SCCOHTs. Transcriptome analyses, further validated by immunohistochemistry, highlighted strong expression of SOX2, a marker that supports the differential diagnosis of these tumors from SMARCA4-deficient lung carcinomas. The prospective recruitment of cases confirmed this new category of 'SMARCA4-deficient thoracic sarcomas' as readily recognizable in clinical practice, providing opportunities to tailor their therapeutic management.
AB - While investigating cohorts of unclassified sarcomas by RNA sequencing, we identified 19 cases with inactivation of SMARCA4, which encodes an ATPase subunit of BAF chromatin-remodeling complexes. Clinically, the cases were all strikingly similar, presenting as compressive mediastino-pulmonary masses in 30- to 35-year-old adults with a median survival time of 7 months. To help define the nosological relationships of these tumors, we compared their transcriptomic profiles with those of SMARCA4-mutated small-cell carcinomas of the ovary, hypercalcemic type (SCCOHTs), SMARCB1-inactivated malignant rhabdoid tumors (MRTs) and lung carcinomas (of which 10% display SMARCA4 mutations). Gene profiling analyses demonstrated that these tumors were distinct from lung carcinomas but related to MRTs and SCCOHTs. Transcriptome analyses, further validated by immunohistochemistry, highlighted strong expression of SOX2, a marker that supports the differential diagnosis of these tumors from SMARCA4-deficient lung carcinomas. The prospective recruitment of cases confirmed this new category of 'SMARCA4-deficient thoracic sarcomas' as readily recognizable in clinical practice, providing opportunities to tailor their therapeutic management.
UR - http://www.scopus.com/inward/record.url?scp=84942992175&partnerID=8YFLogxK
U2 - 10.1038/ng.3399
DO - 10.1038/ng.3399
M3 - Article
C2 - 26343384
AN - SCOPUS:84942992175
SN - 1061-4036
VL - 47
SP - 1200
EP - 1205
JO - Nature Genetics
JF - Nature Genetics
IS - 10
ER -