GLI1 coamplification in well-differentiated/dedifferentiated liposarcomas: Clinicopathologic and molecular analysis of 92 cases Journal Article
| Authors: | Sharma, A. E.; Dickson, M.; Singer, S.; Hameed, M. R.; Agaram, N. P. |
| Article Title: | GLI1 coamplification in well-differentiated/dedifferentiated liposarcomas: Clinicopathologic and molecular analysis of 92 cases |
| Abstract: | GLI1(12q13.3) amplification is identified in a subset of mesenchymal neoplasms with a distinct nested round cell/epithelioid phenotype. MDM2 and CDK4 genes are situated along the oncogenic 12q13-15 segment, amplification of which defines well-differentiated liposarcoma (WDLPS)/dedifferentiated liposarcoma (DDLPS). The 12q amplicon can occasionally include GLI1, a gene in close proximity to CDK4. We hereby describe the first cohort of GLI1/MDM2/CDK4 coamplified WD/DDLPS. The departmental database was queried retrospectively for all cases of WD/DDLPS having undergone next-generation (MSK-IMPACT) sequencing with confirmed MDM2, CDK4, and GLI1 coamplification. Clinicopathologic data was obtained from a review of the medical chart and available histologic material. Four hundred eighty-six WD/DDLPS cases underwent DNA sequencing, 92 (19%) of which harbored amplification of the GLI1 locus in addition to that of MDM2 and CDK4. These included primary tumors (n = 60), local recurrences (n = 29), and metastases (n = 3). Primary tumors were most frequently retroperitoneal (47/60, 78%), mediastinal (4/60, 7%), and paratesticular (3/60, 5%). Average age was 63 years, with a male:female ratio of 3:2. The cohort was comprised of DDLPS (86/92 [93%], 6 of which were WDLPS with early dedifferentiation) and WDLPS without any longitudinal evidence of dedifferentiation (6/92, 7%). One-fifth (13/86, 17%) of DDLPS cases showed no evidence of a well-differentiated component in any of the primary, recurrent, or metastatic specimens. Dedifferentiated areas mostly showed high-grade undifferentiated pleomorphic sarcoma-like (26/86,30%) and high-grade myxofibrosarcoma-like (13/86,16%) morphologies. A disproportionately increased incidence of meningothelial whorls with/without osseous metaplasia was observed as the predominant pattern in 16/86 (19%) cases, and GLI1-altered morphology as described was identified in a total of 10/86 (12%) tumors. JUN (1p32.1), also implicated in the pathogenesis of WD/DDLPS, was coamplified with all 3 of MDM2, CDK4, and GLI1 in 7/91 (8%) cases. Additional loci along chromosomal arms 1p and 6q, including TNFAIP3, LATS1, and ESR1, were also amplified in a subset of cases. In this large-scale cohort of GLI1 coamplified WD/DDLPS, we elucidate uniquely recurrent features including meningothelial whorl-like and GLI-altered morphology in dedifferentiated areas. Assessment of tumor location (retroperitoneal or mediastinal), identification of a well-differentiated liposarcoma component, and coamplification of other spatially discrete genomic segments (1p and 6q) might aid in distinction from tumors with true driver GLI1 alterations. © 2024 United States & Canadian Academy of Pathology |
| Keywords: | adult; controlled study; human tissue; aged; primary tumor; major clinical study; cancer recurrence; metastasis; gene amplification; cohort analysis; gene locus; retrospective study; morphology; dna; amplicon; amplification; transcription factor gli1; cyclin dependent kinase 4; mdm2; cell dedifferentiation; cdk4; dedifferentiated liposarcoma; high throughput sequencing; well differentiated liposarcoma; gli1; well-differentiated liposarcoma; dna sequencing; human; male; female; article; mouse double minute 2 homolog; 12q |
| Journal Title: | Modern Pathology |
| Volume: | 37 |
| Issue: | 6 |
| ISSN: | 0893-3952 |
| Publisher: | Nature Research |
| Date Published: | 2024-06-01 |
| Start Page: | 100494 |
| Language: | English |
| DOI: | 10.1016/j.modpat.2024.100494 |
| PUBMED: | 38621503 |
| PROVIDER: | scopus |
| PMCID: | PMC11193651 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF -- Corresponding author is MSK author: Narasimhan P. Agaram -- Source: Scopus |
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