PATZ1: rearranged sarcomas are well recognized tumors as part of the family of round cell sarcoma with EWSR1-non-ETS fusions. Whether PATZ1-rearranged Central Nervous System (CNS) tumors are a distinct tumor type is debatable. We thoroughly characterized a pediatric series of PATZ1-rearranged CNS tumors by Chromosome Microarray Analysis (CMA), DNA methylation analysis, gene expression profiling and, when frozen tissue available, Optical Genome Mapping (OGM). The series consisted of 7 cases (M:F=1.3:1, 1-17 years, median 12). On MRI, the tumors were supratentorial in close relation to the lateral ventricles (intraventricular or iuxtaventricular), preferentially located in the occipital lobe. Two major histological groups were identified: one (4 cases) with an overall glial appearance, indicated as "neuroepithelial" (NET) by analogy with the corresponding methylation class (MC); the other (3 cases) with a predominant spindle cell sarcoma morphology, indicated as "sarcomatous" (SM). A single distinct methylation cluster encompassing both groups was identified by multidimensional scaling analysis. Despite the epigenetic homogeneity, unsupervised clustering analysis of gene expression profiles revealed 2 distinct transcriptional subgroups correlating with the histological phenotypes. Interestingly, genes implicated in epithelial-mesenchymal transition and extracellular matrix composition were enriched in the subgroup associated to the SM phenotype. The combined use of CMA and OGM enabled the identification of chromosome 22 chromothripsis in all cases suitable for the analyses, explaining the physical association of PATZ1 to EWSR1 or MN1. Six patients are currently disease-free (median follow-up 30 months, range12-92). One patient of the SM-group developed spinal metastases at 26 months from diagnosis and is currently receiving multimodal therapy (42 months). Our data suggest that PATZ1-CNS tumors are defined by chromosome 22 chromothripsis as causative of PATZ1 fusion, show peculiar MRI features (e.g., relation to lateral ventricles, supratentorial frequently posterior site), and, although epigenetically homogeneous, encompass 2 distinct histological and transcriptional subgroups.
PATZ1-rearranged tumors of the central nervous system: characterization of a pediatric series of seven cases / Rossi, Sabrina; Barresi, Sabina; Stefania Colafati, Giovanna; Genovese, Silvia; Tancredi, Chantal; Costabile, Valentino; Patrizi, Sara; Giovannoni, Isabella; Asioli, Sofia; Luigi Poliani, Pietro; Paola Gardiman, Marina; Cardoni, Antonello; DEL BALDO, Giada; Antonelli, Manila; Gianno, Francesca; Piccirilli, Eleonora; Catino, Giorgia; Martucci, Licia; Quacquarini, Denise; Toni, Francesco; Melchionda, Fraia; Viscardi, Elisabetta; Zucchelli, Mino; Dal Pos, Sandro; Gatti, Enza; Liserre, Roberto; Schiavello, Elisabetta; Diomedi-Camassei, Francesca; Carai, Andrea; Mastronuzzi, Angela; Gessi, Marco; Giannini, Caterina; Novelli, Antonio; ONETTI MUDA, Andrea; Miele, Evelina; Alesi, Viola; Alaggio, Rita. - In: MODERN PATHOLOGY. - ISSN 0893-3952. - 37:2(2023). [10.1016/j.modpat.2023.100387]
PATZ1-rearranged tumors of the central nervous system: characterization of a pediatric series of seven cases
Antonello Cardoni;Giada Del Baldo;Manila Antonelli;Francesca Gianno;Denise Quacquarini;Francesco Toni;Fraia Melchionda;Angela Mastronuzzi;Antonio Novelli;Andrea Onetti Muda;Evelina Miele;Rita Alaggio
2023
Abstract
PATZ1: rearranged sarcomas are well recognized tumors as part of the family of round cell sarcoma with EWSR1-non-ETS fusions. Whether PATZ1-rearranged Central Nervous System (CNS) tumors are a distinct tumor type is debatable. We thoroughly characterized a pediatric series of PATZ1-rearranged CNS tumors by Chromosome Microarray Analysis (CMA), DNA methylation analysis, gene expression profiling and, when frozen tissue available, Optical Genome Mapping (OGM). The series consisted of 7 cases (M:F=1.3:1, 1-17 years, median 12). On MRI, the tumors were supratentorial in close relation to the lateral ventricles (intraventricular or iuxtaventricular), preferentially located in the occipital lobe. Two major histological groups were identified: one (4 cases) with an overall glial appearance, indicated as "neuroepithelial" (NET) by analogy with the corresponding methylation class (MC); the other (3 cases) with a predominant spindle cell sarcoma morphology, indicated as "sarcomatous" (SM). A single distinct methylation cluster encompassing both groups was identified by multidimensional scaling analysis. Despite the epigenetic homogeneity, unsupervised clustering analysis of gene expression profiles revealed 2 distinct transcriptional subgroups correlating with the histological phenotypes. Interestingly, genes implicated in epithelial-mesenchymal transition and extracellular matrix composition were enriched in the subgroup associated to the SM phenotype. The combined use of CMA and OGM enabled the identification of chromosome 22 chromothripsis in all cases suitable for the analyses, explaining the physical association of PATZ1 to EWSR1 or MN1. Six patients are currently disease-free (median follow-up 30 months, range12-92). One patient of the SM-group developed spinal metastases at 26 months from diagnosis and is currently receiving multimodal therapy (42 months). Our data suggest that PATZ1-CNS tumors are defined by chromosome 22 chromothripsis as causative of PATZ1 fusion, show peculiar MRI features (e.g., relation to lateral ventricles, supratentorial frequently posterior site), and, although epigenetically homogeneous, encompass 2 distinct histological and transcriptional subgroups.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
