dataset
posted on 2023-03-31, 22:31 authored by Alvin P. Makohon-Moore, Evan J. Lipson, Jody E. Hooper, Amanda Zucker, Jungeui Hong, Craig M. Bielski, Akimasa Hayashi, Collin Tokheim, Priscilla Baez, Rajya Kappagantula, Zachary Kohutek, Vladimir Makarov, Nadeem Riaz, Michael A. Postow, Paul B. Chapman, Rachel Karchin, Nicholas D. Socci, David B. Solit, Timothy A. Chan, Barry S. Taylor, Suzanne L. Topalian, Christine A. Iacobuzio-Donahue Supplementary Tables S1-S8 show the samples used for study (Table S1), the somatic single nucleotide variants, small insertions and small deletions (Table S2), the somatic copy number alterations anallyzed (Table S3), the gene list used to analyze somatic mutations (Table S4), putative driver genes, immunotherapy related genes, and mutation-targeted therapy genes affected by mutations in each case (Table S5), mutation signatures detected with a cosine score {greater than or equal to}0.80 (Table S6), Jaccard similarity coefficients (Table S7), and putative neoantigens in each case (Table S8).
Funding
Melanoma Research Alliance
Bloomberg-Kimmel Institute for Cancer Immunotherapy
Moving for Melanoma of Delaware
NCI
MSKCC TROT
Pershing Square Sohn Cancer Research
History
ARTICLE ABSTRACT
Melanoma is a biologically heterogeneous disease composed of distinct clinicopathologic subtypes that frequently resist treatment. To explore the evolution of treatment resistance and metastasis, we used a combination of temporal and multilesional tumor sampling in conjunction with whole-exome sequencing of 110 tumors collected from 7 patients with cutaneous (n = 3), uveal (n = 2), and acral (n = 2) melanoma subtypes.
Primary tumors, metastases collected longitudinally, and autopsy tissues were interrogated. All but 1 patient died because of melanoma progression.
For each patient, we generated phylogenies and quantified the extent of genetic diversity among tumors, specifically among putative somatic alterations affecting therapeutic resistance.
In 4 patients who received immunotherapy, we found 1–3 putative acquired and intrinsic resistance mechanisms coexisting in the same patient, including mechanisms that were shared by all tumors within each patient, suggesting that future therapies directed at overcoming intrinsic resistance mechanisms may be broadly effective.
