Cohesin gene mutations in tumorigenesis: from discovery to clinical significance
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Cohesin is a multi-protein complex composed of four coresubunits (SMC1A, SMC3, RAD21, and either STAG1 orSTAG2) that is responsible for the cohesion of sisterchromatids following DNA replication until its cleavage duringmitosis thereby enabling faithful segregation of sisterchromatids into two daughter cells. Recent cancer genomicsanalyses have discovered a high frequency of somaticmutations in the genes encoding the core cohesin subunits aswell as cohesin regulatory factors (e.g. NIPBL, PDS5B, ESPL1)in a select subset of human tumors including glioblastoma,Ewing sarcoma, urothelial carcinoma, acute myeloidleukemia, and acute megakaryoblastic leukemia. Herein wereview these studies including discussion of the functionalsignificance of cohesin inactivation in tumorigenesis andpotential therapeutic mechanisms to selectively target cancersharboring cohesin mutations.
Abstract
Cohesin is a multi-protein complex composed of four coresubunits (SMC1A, SMC3, RAD21, and either STAG1 orSTAG2) that is responsible for the cohesion of sisterchromatids following DNA replication until its cleavage duringmitosis thereby enabling faithful segregation of sisterchromatids into two daughter cells. Recent cancer genomicsanalyses have discovered a high frequency of somaticmutations in the genes encoding the core cohesin subunits aswell as cohesin regulatory factors (e.g. NIPBL, PDS5B, ESPL1)in a select subset of human tumors including glioblastoma,Ewing sarcoma, urothelial carcinoma, acute myeloidleukemia, and acute megakaryoblastic leukemia. Herein wereview these studies including discussion of the functionalsignificance of cohesin inactivation in tumorigenesis andpotential therapeutic mechanisms to selectively target cancersharboring cohesin mutations.
참고문헌 (69)
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