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Integrating Next Generation Sequencing with Morphology Improves Prognostic and Biologic Classification of Spitz Neoplasms

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE142443 | GEO | 2020/02/26

REPOSITORIES: GEO

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Integrating Next Generation Sequencing with Morphology Improves Prognostic and Biologic Classification of Spitz Neoplasms [RNA-Seq]

Project description:The newest WHO classification suggests eliminating cases with BRAF and NRAS mutations from the categories of Spitz tumors (ST) and Spitz melanoma (SM). We aimed to better characterize the genomics of Spitz neoplasms and assess whether integrating genomic data with morphologic diagnosis improves classification and prognostication. We performed DNA and RNA sequencing on 80 STs, 26 SMs, and 22 melanomas with Spitzoid features (MSF). NGS data was used to reclassify tumors by moving BRAF/NRAS-mutated cases to MSF. Eighty-one percent of STs harbored kinase fusions/truncations. Of SMs, 77% had fusions/truncations, 8 involving MAP3K8. Novel fusions identified were MYO5A-FGFR1, MYO5A-ERBB4, and PRKDC-CTNNB1. The majority of MSFs (84%) had BRAF, NRAS, or NF1 mutations, and 62% had TERT promoter mutations. Only after reclassification, the following was observed: 1) mRNA expression showed distinct clustering of MSF; 2) 6/7 cases with recurrence and all distant metastases were MSFs; 3) RFS was worse in MSF than ST and SM groups (p=0.0073); 4) classification incorporating genomic data was highly predictive of recurrence (OR 13.20, p=0.0197). The majority of STs and SMs have kinase fusions as primary initiating genomic events. Eliminating BRAF/NRAS-mutated neoplasms from these categories results in improved classification and prognostication of melanocytic neoplasms with Spitzoid cytomorphology.

2020-02-26 | GSE142441 | GEO

Integrating Next Generation Sequencing with Morphology Improves Prognostic and Biologic Classification of Spitz Neoplasms [DNA-Seq]

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Integrating Next Generation Sequencing with Morphology Improves Prognostic and Biologic Classification of Spitz Neoplasms

Project description:Integrating Next Generation Sequencing with Morphology Improves Prognostic and Biologic Classification of Spitz Neoplasms

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Integrating Next Generation Sequencing with Morphology Improves Prognostic and Biologic Classification of Spitz Neoplasms [DNA-Seq]

Project description:Integrating Next Generation Sequencing with Morphology Improves Prognostic and Biologic Classification of Spitz Neoplasms [DNA-Seq]

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Integrating Next Generation Sequencing with Morphology Improves Prognostic and Biologic Classification of Spitz Neoplasms [RNA-Seq]

Project description:Integrating Next Generation Sequencing with Morphology Improves Prognostic and Biologic Classification of Spitz Neoplasms [RNA-Seq]

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