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Genomic and Transcriptomic Analysis Reveals Incremental Disruption of Key Signaling Pathways during Melanoma Evolution.

Abstract：

:We elucidated genomic and transcriptomic changes that accompany the evolution of melanoma from pre-malignant lesions by sequencing DNA and RNA from primary melanomas and their adjacent precursors, as well as matched primary tumors and regional metastases. In total, we analyzed 230 histopathologically distinct areas of melanocytic neoplasia from 82 patients. Somatic alterations sequentially induced mitogen-activated protein kinase (MAPK) pathway activation, upregulation of telomerase, modulation of the chromatin landscape, G1/S checkpoint override, ramp-up of MAPK signaling, disruption of the p53 pathway, and activation of the PI3K pathway; no mutations were specifically associated with metastatic progression, as these pathways were perturbed during the evolution of primary melanomas. UV radiation-induced point mutations steadily increased until melanoma invasion, at which point copy-number alterations also became prevalent.

journal_name

Cancer Cell

journal_title

Cancer cell

authors

Shain AH,Joseph NM,Yu R,Benhamida J,Liu S,Prow T,Ruben B,North J,Pincus L,Yeh I,Judson R,Bastian BC

doi

10.1016/j.ccell.2018.06.005

subject

Has Abstract

pub_date

2018-07-09 00:00:00

pages

45-55.e4

issue

1

eissn

1535-6108

issn

1878-3686

pii

S1535-6108(18)30262-9

journal_volume

34

pub_type

杂志文章

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