SMARCA4 inactivation defines a group of undifferentiated thoracic malignancies transcriptionally related to BAF-deficient sarcomas - Université de Lorraine Access content directly
Journal Articles Nature Genetics Year : 2015

SMARCA4 inactivation defines a group of undifferentiated thoracic malignancies transcriptionally related to BAF-deficient sarcomas

Sarah Watson
  • Function : Author
  • PersonId : 917114
Daniel Pissaloux
  • Function : Author
  • PersonId : 768539
  • IdRef : 17847147X
Sandrine Boyault
  • Function : Author
  • PersonId : 757688
  • IdRef : 075706466
Marie Brevet
  • Function : Author
  • PersonId : 1202971

Abstract

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.
No file

Dates and versions

hal-01684775 , version 1 (15-01-2018)

Identifiers

Cite

Francois Le Loarer, Sarah Watson, Gaëlle Pierron, Vincent Thomas de Montpreville, Stelly Ballet, et al.. SMARCA4 inactivation defines a group of undifferentiated thoracic malignancies transcriptionally related to BAF-deficient sarcomas. Nature Genetics, 2015, 47 (10), pp.1200 - 1205. ⟨10.1038/ng.3399⟩. ⟨hal-01684775⟩
464 View
0 Download

Altmetric

Share

Gmail Facebook X LinkedIn More