The Molecular Evolution of Melanoma Distant Metastases.

Autor:	Bezrookove V; Center for Melanoma Research and Treatment, California Pacific Medical Center, San Francisco, California, USA; California Pacific Medical Center Research Institute, San Francisco, California, USA., Kianian S; Center for Melanoma Research and Treatment, California Pacific Medical Center, San Francisco, California, USA; California Pacific Medical Center Research Institute, San Francisco, California, USA., McGeever L; California Pacific Medical Center Research Institute, San Francisco, California, USA., Jones R; California Pacific Medical Center Research Institute, San Francisco, California, USA., Caressi C; Center for Melanoma Research and Treatment, California Pacific Medical Center, San Francisco, California, USA; California Pacific Medical Center Research Institute, San Francisco, California, USA., Nosrati M; Center for Melanoma Research and Treatment, California Pacific Medical Center, San Francisco, California, USA; California Pacific Medical Center Research Institute, San Francisco, California, USA., Kim KB; Center for Melanoma Research and Treatment, California Pacific Medical Center, San Francisco, California, USA; California Pacific Medical Center Research Institute, San Francisco, California, USA., Leong SP; Center for Melanoma Research and Treatment, California Pacific Medical Center, San Francisco, California, USA; California Pacific Medical Center Research Institute, San Francisco, California, USA., Miller JR 3rd; Center for Melanoma Research and Treatment, California Pacific Medical Center, San Francisco, California, USA; California Pacific Medical Center Research Institute, San Francisco, California, USA., Desprez PY; California Pacific Medical Center Research Institute, San Francisco, California, USA., Kashani-Sabet M; Center for Melanoma Research and Treatment, California Pacific Medical Center, San Francisco, California, USA; California Pacific Medical Center Research Institute, San Francisco, California, USA. Electronic address: kashani@cpmcri.org.
Jazyk:	angličtina
Zdroj:	The Journal of investigative dermatology [J Invest Dermatol] 2024 Nov; Vol. 144 (11), pp. 2530-2540.e1. Date of Electronic Publication: 2024 Apr 04.
DOI:	10.1016/j.jid.2024.03.029
Abstrakt:	The evolution of primary melanoma to lymph node and distant metastasis is incompletely understood. We examined the genomic diversity in melanoma progression in matched primary melanomas and lymph node and distant metastases from 17 patients. FISH analysis revealed cancer cell fractions with monotonic copy number alterations, including PHIP gain and PTEN loss, in the metastatic cascade. By contrast, the cancer cell fraction with copy number alterations for BPTF and MITF was reduced in lymph node metastases but increased in distant metastases. Separately, the cancer cell fraction with NCOA3 copy number alteration was comparable between primary tumors and lymph node metastases yet increased in distant metastases. These results suggest enrichment of the phosphoinositide 3-kinase and MITF pathways in the transition through the metastatic cascade. By contrast, next-generation sequencing analysis did not identify a consistent pattern of changes in variant allele frequency while revealing several intriguing findings, including decreased variant allele frequency in distant metastases and distinct drivers in lymph node versus distant metastases. These results provide evidence that distant melanoma metastasis does not always emanate from lymph node metastasis. These results enhance our understanding of clonal patterns of melanoma metastasis, with possible implications for targeted therapy and metastasis competency. (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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