matrix-associated actin-dependent regulator of chromatin subfamily a member 4
mutations associated with small-cell carcinoma of the ovary, hypercalcemia
Genetic studies suggest
loss-of-function mutations in SMARCA4 could help diagnose SCCOHT.
Mutations in the chromatin remodeling gene SMARCA4 were identified in
patients from three families using whole-genome sequencing, and the
association was validated in an additional affected family, preserved tumor
samples and a SCCOHT cell line. Loss of SMARCA4 was also detected in
38 of 43 SCCOHT tumor samples but only 1 of 139 samples of other ovarian
tumors. In an independent analysis of 12 SCCOHT samples, exome sequencing
identified SMARCA4 mutations in all tumors, and immunohistochemistry
studies on 9 of the samples showed decreased expression of the protein
compared with that in samples from healthy controls. In non-small cell lung
cancer (NSCLC) cells lacking SMARCA4, ectopic expression of the gene
decreased tumor growth. In a separate study, 9 of 12 SCCOHT tumor and patient
germline tissue samples had SMARCA4 mutations, and 14 of 17 SCCOHT
tumors showed loss of SMARCA4 protein expression. Next steps include
identifying strategies to treat patients with the mutations.
Published online April 24, 2014
For first study, findings
unpatented; licensing status not applicable
Patent application filed for findings in second study; available for
Patent and licensing status unavailable for findings in third study
Witkowski, L. et al.
Nat. Genet.; published online March 23, 2013;
Contact: William D. Foulkes, McGill University, Montreal,
Jelinic, P. et al. Nat. Genet.; published online March 23, 2014;
Contact: Douglas A. Levine, Memorial Sloan Kettering Cancer
Center, New York, N.Y.
Ramos, P. et al. Nat. Genet.; published online March 23, 2014;
Contact: Jeffrey M. Trent, The Translational Genomics
Research Institute, Phoenix, Ariz.
Contact: David G. Huntsman, The University of British
Columbia, Vancouver, British Columbia, Canada