Dataset Information

Landscape of mutations in early stage primary cutaneous melanoma: An InterMEL study.

ABSTRACT: It is unclear why some melanomas aggressively metastasize while others remain indolent. Available studies employing multi-omic profiling of melanomas are based on large primary or metastatic tumors. We examine the genomic landscape of early-stage melanomas diagnosed prior to the modern era of immunological treatments. Untreated cases with Stage II/III cutaneous melanoma were identified from institutions throughout the United States, Australia and Spain. FFPE tumor sections were profiled for mutation, methylation and microRNAs. Preliminary results from mutation profiling and clinical pathologic correlates show the distribution of four driver mutation sub-types: 31% BRAF; 18% NRAS; 21% NF1; 26% Triple Wild Type. BRAF mutant tumors had younger age at diagnosis, more associated nevi, more tumor infiltrating lymphocytes, and fewer thick tumors although at generally more advanced stage. NF1 mutant tumors were frequent on the head/neck in older patients with severe solar elastosis, thicker tumors but in earlier stages. Triple Wild Type tumors were predominantly male, frequently on the leg, with more perineural invasion. Mutations in TERT, TP53, CDKN2A and ARID2 were observed often, with TP53 mutations occurring particularly frequently in the NF1 sub-type. The InterMEL study will provide the most extensive multi-omic profiling of early-stage melanoma to date. Initial results demonstrate a nuanced understanding of the mutational and clinicopathological landscape of these early-stage tumors.

SUBMITTER: Luo L

PROVIDER: S-EPMC9640183 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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Landscape of mutations in early stage primary cutaneous melanoma: An InterMEL study.

Luo Li L Shen Ronglai R Arora Arshi A Orlow Irene I Busam Klaus J KJ Lezcano Cecilia C Lee Tim K TK Hernando Eva E Gorlov Ivan I Amos Christopher C Ernstoff Marc S MS Seshan Venkatraman E VE Cust Anne E AE Wilmott James J Scolyer Richard A RA Mann Graham G Nagore Eduardo E Funchain Pauline P Ko Jennifer J Ngo Peter P Edmiston Sharon N SN Conway Kathleen K Googe Paul B PB Ollila David D Lee Jeffrey E JE Fang Shenying S Rees Judy R JR Thompson Cheryl L CL Gerstenblith Meg M Bosenberg Marcus M Gould Rothberg Bonnie B Osman Iman I Saenger Yvonne Y Reynolds Adam Z AZ Schwartz Matthew M Boyce Tawny T Holmen Sheri S Brunsgaard Elise E Bogner Paul P Kuan Pei Fen PF Wiggins Charles C Thomas Nancy E NE Begg Colin B CB Berwick Marianne M

Pigment cell & melanoma research 20220812 6

It is unclear why some melanomas aggressively metastasize while others remain indolent. Available studies employing multi-omic profiling of melanomas are based on large primary or metastatic tumors. We examine the genomic landscape of early-stage melanomas diagnosed prior to the modern era of immunological treatments. Untreated cases with Stage II/III cutaneous melanoma were identified from institutions throughout the United States, Australia and Spain. FFPE tumor sections were profiled for muta ...[more]

PMID: 35876628

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Project description:Background. Consensus on standardized active surveillance or follow-up care by clinicians is lacking leading to considerable variation in practice across countries. An important structural modelling consideration is that self-examination by patients and their partners can detect melanoma recurrence outside of active surveillance regimes. Objectives. To identify candidate melanoma surveillance strategies for American Joint Committee on Cancer (AJCC) stage I disease and compare them with the current recommended practice in a cost-utility analysis framework. Methods. In consultation with UK clinical experts, a microsimulation model was built in TreeAge Pro 2019 R1.0 (Williamstown, MA, USA) to evaluate surveillance strategies for AJCC stage IA and IB melanoma patients separately. The model incorporated patient behaviors such as self-detection and emergency visits to examine suspicious lesions. A National Health Service (NHS) perspective was taken. Model input parameters were taken from the literature and where data were not available, local expert opinion was sought. Probabilistic sensitivity analysis, one-way sensitivity analysis on pertinent parameters and value of information was performed. Results. In the base-case probabilistic sensitivity analysis, less intensive surveillance strategies for AJCC stage IA and IB had lower total lifetime costs than the current National Institute for Health and Care Excellence (NICE) recommended strategy with similar effectiveness in terms of quality-adjusted life years and thereby likely to be cost-effective. Many strategies had similar effectiveness due to the relatively low chance of recurrence and the high rate of self-detection. Sensitivity and scenario analyses did not change these findings. Conclusions. Our model findings suggest that less resource intensive surveillance may be cost-effective compared with the current NICE surveillance guidelines. However, to advocate convincingly for changes, better evidence is required.

Dataset Information

Landscape of mutations in early stage primary cutaneous melanoma: An InterMEL study.

Publications

Landscape of mutations in early stage primary cutaneous melanoma: An InterMEL study.

Similar Datasets

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