In:
Genes, Chromosomes and Cancer, Wiley
Abstract:
High‐mobility group AT‐hook 2 ( HMGA2 ) is rearranged in various types of mesenchymal tumors, particularly lipomas. HMGA2 is also co‐amplified with mouse double minute 2 ( MDM2 ) in well‐differentiated liposarcoma/dedifferentiated liposarcoma (WDLPS/DDLPS). We report a case of relapsed DDLPS with a novel in‐frame fusion between HMGA2 and KITLG , which encodes the ligand for KIT kinase, a critical protein involved in gametogenesis, hematopoiesis, and melanogenesis. The HMGA2 breakpoint is in intron 3, a commonly observed location for HMGA2 rearrangements, while the KITLG breakpoint is in intron 2, leading to a fusion protein that contains almost the entire coding sequence of KITLG . By immunohistochemical staining, tumor cells expressed KIT and showed phosphorylated MAPK, a major KIT downstream target. We suggest an oncogenic mechanism that involves the overexpression of KITLG caused by its rearrangement with HMGA2 , leading to the constitutive activation of KIT kinase. While MDM2 amplification was observed in both the primary tumor and the relapsed tumor, the HMGA2::KITLG was only present in the relapsed tumor, indicating the role of HMGA2::KITLG in disease progression.
Type of Medium:
Online Resource
ISSN:
1045-2257
,
1098-2264
Language:
English
Publisher:
Wiley
Publication Date:
2023
detail.hit.zdb_id:
1018988-9
detail.hit.zdb_id:
1492641-6
SSG:
12
