Unknown

Dataset Information

0

KMT2D/MLL2 inactivation is associated with recurrence in adult-type granulosa cell tumors of the ovary.


ABSTRACT: Adult-type granulosa cell tumors of the ovary (aGCTs) are rare gynecologic malignancies that exhibit a high frequency of somatic FOXL2 c.C402G (p.Cys134Trp) mutation. Treatment of relapsed aGCT remains a significant clinical challenge. Here we show, using whole-exome and cancer gene panel sequencing of 79 aGCTs from two independent cohorts, that truncating mutation of the histone lysine methyltransferase gene KMT2D (also known as MLL2) is a recurrent somatic event in aGCT. Mono-allelic KMT2D-truncating mutations are more frequent in recurrent (10/44, 23%) compared with primary (1/35, 3%) aGCTs (p?=?0.02, two-sided Fisher's exact test). IHC detects additional non-KMT2D-mutated aGCTs with loss of nuclear KMT2D expression, suggesting that non-genetic KMT2D inactivation may occur in this tumor type. These findings identify KMT2D inactivation as a novel driver event in aGCTs and suggest that mutation of this gene may increase the risk of disease recurrence.

SUBMITTER: Hillman RT 

PROVIDER: S-EPMC6021426 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

altmetric image

Publications


Adult-type granulosa cell tumors of the ovary (aGCTs) are rare gynecologic malignancies that exhibit a high frequency of somatic FOXL2 c.C402G (p.Cys134Trp) mutation. Treatment of relapsed aGCT remains a significant clinical challenge. Here we show, using whole-exome and cancer gene panel sequencing of 79 aGCTs from two independent cohorts, that truncating mutation of the histone lysine methyltransferase gene KMT2D (also known as MLL2) is a recurrent somatic event in aGCT. Mono-allelic KMT2D-tru  ...[more]

Similar Datasets

| S-EPMC7390666 | biostudies-literature
| S-EPMC8072996 | biostudies-literature
| EGAS00001005414 | EGA
| S-EPMC8909001 | biostudies-literature
| S-EPMC5447140 | biostudies-literature
| S-EPMC8928977 | biostudies-literature
| EGAS00001002833 | EGA
| S-EPMC4924709 | biostudies-literature
| S-EPMC5669801 | biostudies-literature
| S-EPMC4222524 | biostudies-literature