FISH Diagnostic Assessment of MDM2 Amplification in Liposarcoma: Potential Pitfalls and Troubleshooting Recommendations

Gambella, Alessandro; Bertero, Luca; Rondón-Lagos, Milena; Cantogno, Ludovica Verdun di; Rangel, Nelson; Pitino, Chiara; Ricci, Alessia Andrea; Mangherini, Luca; Castellano, Isabella; Cassoni, Paola

doi:10.3390/ijms24021342

Cited by 11 publications

(5 citation statements)

References 69 publications

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“…12,13 MDM2 amplification acts as an oncogenic role in several malignant tumors. 14 This is the first case report in which MDM2 amplification has been found in combined hepatocellular-cholangiocarcinoma. Thus, the pathogenic significance of MDM2 amplification in combined hepatocellular-cholangiocarcinoma has not been elucidated.…”

Section: Discussionmentioning

confidence: 79%

Combined Hepatocellular-Cholangiocarcinoma With Ductal Plate Malformation Pattern: A Case Report With Molecular Analysis

Moon

Song

et al. 2023

Int J Surg Pathol

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Combined hepatocellular-cholangiocarcinoma with a ductal plate malformation pattern is an extremely rare entity with unelucidated pathogenesis. We present the case of a 60-year-old male patient who underwent a sectionectomy for pre-operative diagnosis of hepatocellular carcinoma based on clinical and image findings. Gross examination of the specimen revealed a well-defined tumor with cystic change measuring 6.7 × 6.2 cm. Microscopically, the lesion had classical features of hepatocellular carcinoma and intrahepatic cholangiocarcinoma exhibited neoplastic glands with irregular-sized dilated lumens, resembling a ductal plate malformation. Postoperative diagnosis was combined hepatocellular-cholangiocarcinoma with ductal plate malformation pattern. Next-generation sequencing revealed genomic alteration in 15 genes: CDKN2A, CHD4, CYP2D6, ERBB3, KIR3DL1, KRAS, MDM2, PIM1, STAT6, TPMT amplification, FANCD2, FAT1, FLT4, RASA1, and TP53 point mutation. This is the first case report of molecular alteration in combined hepatocellular-cholangiocarcinoma with ductal plate malformation pattern.

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Section: Discussionmentioning

confidence: 79%

Combined Hepatocellular-Cholangiocarcinoma With Ductal Plate Malformation Pattern: A Case Report With Molecular Analysis

Moon

Song

et al. 2023

Int J Surg Pathol

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“…MDM2 , YAP1 and IGF1R , which could provide leads for targeted therapies [23]. Moreover, previous studies found that MDM2 was among the oncogenes most often amplified as circular ecDNA across cancer types [15, 36]. Not only did circular amplicons achieve higher CNs, also the oncogene expression was higher corrected for CN due to increased chromatin accessibility and possible enhancer rewiring [15].…”

Section: Discussionmentioning

confidence: 99%

Complex structural variation is prevalent and highly pathogenic in pediatric solid tumors

van Belzen,

van Tuil,

Badloe

et al. 2023

Preprint

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Background: In pediatric cancer, structural variants (SVs) and copy number alterations can contribute to cancer initiation and progression, and hence aid diagnosis and treatment stratification. The few studies into complex rearrangements have found associations with tumor aggressiveness or poor outcome. Yet, their prevalence and biological relevance across pediatric solid tumors remains unknown. Results: In a cohort of 120 primary tumors, we systematically characterized patterns of extrachromosomal DNA, chromoplexy and chromothripsis across five pediatric solid cancer types: neuroblastoma, Ewing sarcoma, Wilms tumor, hepatoblastoma and rhabdomyosarcoma. Complex SVs were identified in 56 tumors (47%) and different classes occurred across multiple cancer types. Recurrently mutated regions tend to be cancer-type specific and overlap with cancer genes, suggesting that selection contributes to shaping the SV landscape. In total, we identified potentially pathogenic complex SVs in 42 tumors that affect cancer driver genes or result in unfavorable chromosomal alterations. Half of which were known drivers, e.g. MYCN amplifications due to ecDNA and EWSR1::FLI1 fusions due to chromoplexy. Recurrent novel candidate complex events include chromoplexy in WT1 in Wilms tumors, focal chromothripsis with 1p loss in hepatoblastomas and complex MDM2 amplifications in rhabdomyosarcomas. Conclusions: Complex SVs are prevalent and pathogenic in pediatric solid tumors. They represent a type of genomic variation which currently remains unexplored. Moreover, carrying complex SVs seems to be associated with adverse clinical events. Our study highlights the potential for complex SVs to be incorporated in risk stratification or exploited for targeted treatments.

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“…FISH assessment was conducted in accordance with the MDM2 amplification patterns observed in human liposarcoma 22 . A MDM2/GMCL1 ratio higher than 2 was considered indicative of MDM2 amplification.…”

Section: Methodsmentioning

confidence: 99%

Analysis of MDM2 and TP53 genes in canine liposarcoma

Muscatello,

de Biase,

Maloberti

et al. 2024

Sci Rep

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Canine liposarcoma is an uncommon tumor that shares morphological similarities with its human counterpart. In dogs, the genetic features of this tumor are unknown and, based on immunohistochemical studies, amplification of the gene MDM2 and the mutation of TP53 are suspected. In this study 51 cases of primary liposarcomas were immunohistochemically stained for MDM2 and p53 and subjected to fluorescent in situ hybridization and next-generation sequencing to detect MDM2 amplification and TP53 mutations, respectively. MDM2 and p53 were expressed in 21 and 6 cases, respectively. MDM2 amplification and TP53 mutations were identified in 10 and 15 cases, respectively. Statistical analysis revealed an association of the myxoid subtype and the mitotic count with p53 expression and TP53 mutation. No association was found between MDM2 amplification and MDM2 expression or tumor subtype. These results suggest that despite morphological similarities, canine liposarcoma differs from its human counterpart, for which MDM2 amplification is diagnostic for well differentiated and de-differentiated variants, and TP53 mutations are more common in pleomorphic liposarcoma rather than the myxoid one as occur in our cases. Furthermore, canine myxoid liposarcoma likely represents a distinct disease rather than a mere morphological variant.

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FISH Diagnostic Assessment of MDM2 Amplification in Liposarcoma: Potential Pitfalls and Troubleshooting Recommendations

Cited by 11 publications

References 69 publications

Combined Hepatocellular-Cholangiocarcinoma With Ductal Plate Malformation Pattern: A Case Report With Molecular Analysis

Combined Hepatocellular-Cholangiocarcinoma With Ductal Plate Malformation Pattern: A Case Report With Molecular Analysis

Complex structural variation is prevalent and highly pathogenic in pediatric solid tumors

Analysis of MDM2 and TP53 genes in canine liposarcoma

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