Myxoid pleomorphic liposarcoma is distinguished from other liposarcomas by widespread loss of heterozygosity and significantly worse overall survival: A genomic and clinicopathologic study Journal Article

   

Authors:	Dermawan, J. K.; Hwang, S.; Wexler, L.; Tap, W. D.; Singer, S.; Vanderbilt, C. M.; Antonescu, C. R.
Article Title:	Myxoid pleomorphic liposarcoma is distinguished from other liposarcomas by widespread loss of heterozygosity and significantly worse overall survival: A genomic and clinicopathologic study
Abstract:	Myxoid pleomorphic liposarcoma (MPLPS) is a recently described and extremely rare subtype of liposarcoma with a predilection for the mediastinum. However, the genomic features of MPLPS remain poorly understood. We performed comprehensive genomic profiling of MPLPS in comparison with pleomorphic liposarcoma (PLPS) and myxoid/round cell liposarcoma (MRLPS). Of the 8 patients with MPLPS, 5 were female and 3 were male, with a median age of 32 years old (range 10–68). All except one were located in the mediastinum, with invasion of surrounding anatomic structures, including chest wall, pleura, spine, and large vessels. All cases showed an admixture of morphologies reminiscent of PLPS and MRLPS, including myxoid areas with plexiform vasculature admixed with uni- and/or multivacuolated pleomorphic lipoblasts. Less common features included well-differentiated liposarcoma-like areas, and in one case fascicular spindle cell sarcoma reminiscent of dedifferentiated LPS. Clinically, 4 experienced local recurrence, 4 had distant metastases and 5 died of disease. Compared to PLPS and MRLPS, patients with MPLPS had worse overall and progression-free survival. Recurrent TP53 mutations were present in all 8 MPLPS cases. In contrast, in PLPS, which also showed recurrent TP53 mutations (83%), RB1 and ATRX losses were more common. MRLPS was highly enriched in TERT promoter mutations (88%) and PI3K/AKT pathway mutations. Copy number profiling in MPLPS revealed multiple chromosomal gains with recurrent amplifications of chromosomes 1, 19 and 21. Importantly, allele-specific copy number analysis revealed widespread loss of heterozygosity (80% of the genome on average) in MPLPS, but not in PLPS or MRLPS. Our findings revealed genome-wide loss of heterozygosity co-existing with TP53 mutations as a characteristic genomic signature distinct from other liposarcoma subtypes, which supports the current classification of MPLPS as a stand-alone pathologic entity. These results further expand the clinicopathologic features of MPLPS, including older age, extra-mediastinal sites, and a highly aggressive outcome. © 2022, The Author(s), under exclusive licence to United States & Canadian Academy of Pathology.
Keywords:	protein kinase b; adolescent; adult; child; clinical article; school child; aged; middle aged; cancer surgery; young adult; unclassified drug; gene mutation; overall survival; promoter region; genetics; clinical feature; doxorubicin; gemcitabine; cancer radiotherapy; comparative study; chromosome 1; chromosome 19; dacarbazine; ipilimumab; progression free survival; gene amplification; protein; cohort analysis; pathology; phosphatidylinositol 3 kinase; protein p53; distant metastasis; ifosfamide; docetaxel; spine; proto-oncogene proteins c-akt; telomerase reverse transcriptase; genomics; recurrent disease; lipopolysaccharide; heterozygosity loss; mesna; trabectedin; spindle cell sarcoma; loss of heterozygosity; mediastinum; chromosome 21; thorax wall; pleura; liposarcoma; eribulin; myxosarcoma; cell vacuole; anatomical variation; copy number variation; phosphatidylinositol 3-kinases; lipopolysaccharides; olaratumab; pi3k/akt signaling; liposarcoma, myxoid; nivolumab; humans; human; male; female; article; rb1 protein; transcriptional regulator atrx; myxoid pleomorphic liposarcoma; myxoid round cell liposarcoma
Journal Title:	Modern Pathology
Volume:	35
Issue:	11
ISSN:	0893-3952
Publisher:	Nature Research
Date Published:	2022-11-01
Start Page:	1644
End Page:	1655
Language:	English
DOI:	10.1038/s41379-022-01107-6
PUBMED:	35672466
PROVIDER:	scopus
PMCID:	PMC9613513
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85131589662&doi=10.1038%2fs41379-022-01107-6&partnerID=40&md5=a7d3e6bca72aac1eeb1b9f60ebfbac98
Notes:	Article -- Export Date: 1 December 2022 -- Source: Scopus

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