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- Title
Variable Genomic Landscapes of Advanced Melanomas with Heavy Pigmentation.
- Authors
Huang, Richard S P; Tse, Julie Y; Harries, Lukas; Graf, Ryon P; Lin, Douglas I; Murugesan, Karthikeyan; Hiemenz, Matthew C; Parimi, Vamsi; Janovitz, Tyler; Decker, Brennan; Severson, Eric; Levy, Mia A; Ramkissoon, Shakti H; Elvin, Julia A; Ross, Jeffrey S; Williams, Erik A
- Abstract
Background In the current study, we examined the real-world prevalence of highly pigmented advanced melanomas (HPMel) and the clinicopathologic, genomic, and ICPI biomarker signatures of this class of tumors. Materials and Methods Our case archive of clinical melanoma samples for which the ordering physician requested testing for both PD-L1 immunohistochemistry (IHC) and comprehensive genomic profiling (CGP) was screened for HPMel cases, as well as for non-pigmented or lightly pigmented advanced melanoma cases (LPMel). Results Of the 1268 consecutive melanoma biopsies in our archive that had been submitted for PD-L1 IHC, 13.0% (165/1268) were HPMel and 87.0% (1103/1268) were LPMel. In the HPMel cohort, we saw a significantly lower tumor mutational burden (TMB, median 8.8 mutations/Mb) than in the LPMel group (11.4 mut/Mb), although there was substantial overlap. In examining characteristic secondary genomic alterations (GA), we found that the frequencies of GA in TERTp , CDKN2A , TP53 , and PTEN were significantly lower in the HPMel cases than in LPMel. A higher rate of GA in CTNNB1 , APC , PRKAR1A , and KIT was identified in the HPMel cohort compared with LPMel. Conclusions In this study, we quantified the failure rates of melanoma samples for PD-L1 testing due to high melanin pigmentation and showed that CGP can be used in these patients to identify biomarkers that can guide treatment decisions for HPMel patients. Using this practical clinical definition for tumor pigmentation, our results indicate that HPMel are frequent at 13% of melanoma samples, and in general appear molecularly less developed, with a lower TMB and less frequent secondary GA of melanoma progression.
- Subjects
BIOMARKERS; NEVUS; GENETIC mutation; MELANINS; IMMUNOHISTOCHEMISTRY; GENETIC testing; TUMOR classification; CANCER patients; TREATMENT failure; GENOMICS; ANIMAL coloration; GENE expression profiling; DESCRIPTIVE statistics; DECISION making in clinical medicine; LONGITUDINAL method
- Publication
Oncologist, 2022, Vol 27, Issue 8, p655
- ISSN
1083-7159
- Publication type
Article
- DOI
10.1093/oncolo/oyac090