Targeted sequencing of FH-deficient uterine leiomyomas reveals biallelic inactivating somatic fumarase variants and allows characterization of missense variants.

ABSTRACT: Uterine leiomyomas (ULs) constitute a considerable health burden in the general female population. The fumarate hydratase (FH) deficient subtype is found in up to 1.6% and can occur in hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome. We sequenced 13 FH deficient ULs from a previous immunohistochemical screen using a targeted panel and identified biallelic FH variants in all. In eight, we found an FH point mutation (two truncating, six missense) with evidence for loss of the second allele. Variant allele-frequencies in all cases with a point mutation pointed to somatic variants. Spatial clustering of the identified missense variants in the lyase domain indicated altered fumarase oligomerization with subsequent degradation as explanation for the observed FH deficiency. Bi

SUBMITTER: Popp B 

PROVIDER: S-EPMC7581509 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature