Exome sequencing identifies an MLL3 gene germ line mutation in a pedigree of colorectal cancer and acute myeloid leukemia

摘要

Recently, the frequently mutated gene MLL3 was found to be related to the pathogenesis of hepatocellular carcinoma (HCC), fluke-associated cholangiocarcinoma, gastric cancer, and transitional carcinoma of the bladder, raising the possibility that the MLL3 gene and its encoded chromatin remodeling protein MLL3 are etiologically related to cancers. We performed exome sequencing for 4 patients in a multigenerational pedigree with colorectal cancers and acute myeloid leukemia (AML) and identified an insertion mutation in the MLL3 gene on chromosome 7, producing a frame shift leading to a premature truncation at codon 827. To our knowledge, it was the first germ line MLL3 mutation found in a cancer pedigree. Because MLL3 is an enzyme for histone methyl-ation, pharmacologic intervention may be possible.