Leiomyoma with KAT6B-KANSL1 fusion: case report of a rapidly enlarging uterine mass in a postmenopausal woman

Abstract

Background Uterine leiomyomas, in contrast to sarcomas, tend to cease growth following menopause. In the setting of a rapidly enlarging uterine mass in a postmenopausal patient, clinical distinction of uterine leiomyoma from sarcoma is difficult and requires pathologic examination. Case presentation A 74-year-old woman presented with postmenopausal bleeding and acute blood loss requiring transfusion. She was found to have a rapidly enlarging uterine mass clinically suspicious for sarcoma. An abdominal hysterectomy and bilateral salpingo-oophorectomy were performed. A 15.5 cm partially necrotic intramural mass was identified in the uterine corpus. The tumor was classified as a cellular leiomyoma. RNA sequencing identified a KAT6B - KANSL1 fusion that was confirmed by RT-PCR and Sanger sequencing. After 6 months of follow-up, the patient remains asymptomatic without evidence of disease. Conclusion Prior studies of uterine leiomyomas have identified KAT6B ( previously MORF ) rearrangements in uterine leiomyomas, but this case is the first to identify a KAT6B-KANSL1 gene fusion in a uterine leiomyoma. While alterations of MED12 and HMGA2 are most common in uterine leiomyomas, a range of other genetic pathways have been described. Our case contributes to the evolving molecular landscape of uterine leiomyomas.

Integrated mutational landscape analysis of uterine leiomyosarcomas

“…22.5 events per sample (37.0 per Yale sample and 17.1 per TCGA sample). Among them, two known fusion events (i.e., ACTG2-ALK and KAT6B-KANSL1) were reported in LMS (30) and LM (31,32), respectively (Fig. 3A).…”

Molecular and clinicopathologic characterization of intravenous leiomyomatosis

“…Alterations involving 10q have rarely been reported in UL (2%) 49 , although specifically del(10q) are more commonly observed in ULMS than UL 50 . KAT6B , a rare tumor suppressor gene with homozygous deletions in multiple cancer types 51 , 52 , is described as the candidate 10q gene in UL in a study analyzing the rare t(10;17) event 53 and a similar t(10;17), resulting in a KAT6B-KANSL1 fusion detected in a retroperitoneal and more recently in a uterine leiomyoma 54 , 55 . This fusion is located at exon 3 (histone binding domain) of KAT6B without involvement of the downstream functional domains (histone acetylation and transcriptional activation), implicating KAT6B loss of function.…”

Molecular Classification of Endometrial Stromal Sarcomas Using RNA Sequencing Defines Nosological and Prognostic Subgroups with Different Natural History

“…TET2 increases the activity of HDAC2 [31], and mutations of this gene have previously been described in other neoplasms such as AML (acute myeloid leukemia) with an unfavorable prognostic value [32]. In one case (CLB_RNA_1372), we detected a KAT6B-KANSL1 fusion that was previously described in two cases of leiomyomas [33,34]. KAT6B encodes a lysine acetyltransferase involved in histone tail modifications.…”