Mutually exclusive genetic interactions and gene essentiality shape the genomic landscape of primary melanoma

被引：5

作者：

Birkealv, Sofia ^{[1
]}

Harland, Mark ^{[2
]}

Matsuyama, Larissa Satiko Alcantara Sekimoto ^{[1
,3
]}

Rashid, Mamun ^{[1
]}

Mehta, Ishan ^{[1
]}

Laye, Jonathan P. ^{[2
]}

Haase, Kerstin ^{[4
]}

Mell, Tracey ^{[2
]}

Iyer, Vivek ^{[1
]}

Robles-Espinoza, Carla Daniela ^{[1
,5
]}

McDermott, Ultan ^{[1
]}

van Loo, Peter ^{[4
]}

Kuijjer, Marieke L. ^{[6
,7
,8
]}

Possik, Patricia A. ^{[9
]}

Engler, Silvya Stuchi Maria ^{[3
]}

Bishop, D. Timothy ^{[2
]}

Newton-Bishop, Julia ^{[2
]}

Adams, David J. ^{[1
]}

机构：

[1] Wellcome Sanger Inst, Wellcome Trust Genome Campus, Cambridge, England

[2] Univ Leeds, Div Haematol & Immunol, Sch Med, Leeds, W Yorkshire, England

[3] Univ Sao Paulo, Sch Pharmaceut Sci, Dept Clin & Toxicol Anal, Sao Paulo, Brazil

[4] Francis Crick Inst, London, England

[5] Univ Nacl Autonoma Mexico, Lab Int Invest Genoma Humano, Campus Juriquilla, Santiago De Queretaro, Mexico

[6] Univ Oslo, Fac Med, Ctr Mol Med Norway NCMM, Nordic EMBL Partnership, Oslo, Norway

[7] Leiden Univ, Dept Pathol, Med Ctr, Leiden, Netherlands

[8] Leiden Univ, Leiden Ctr Computat Oncol, Med Ctr, Leiden, Netherlands

[9] Brazilian Natl Canc Inst, Div Expt & Translat Res, Rio De Janeiro, Brazil

来源：

JOURNAL OF PATHOLOGY | 2023年 / 259卷 / 01期

基金：

英国惠康基金; 欧洲研究理事会; 英国医学研究理事会;

关键词：

melanoma; gene essentiality; genetic epistasis; genomic landscape; CRISPR screening; interferon regulatory factor 4 (IRF4); genome sequencing; somatic mutation; driver genes; primary cancer; PROMOTER MUTATIONS; CANCER; PROTEIN; PATTERNS; BINDING; COPY; SKIN;

D O I：

10.1002/path.6019

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Melanoma is a heterogenous malignancy with an unpredictable clinical course. Most patients who present in the clinic are diagnosed with primary melanoma, yet large-scale sequencing efforts have focused primarily on metastatic disease. In this study we sequence-profiled 524 American Joint Committee on Cancer Stage I-III primary tumours. Our analysis of these data reveals recurrent driver mutations, mutually exclusive genetic interactions, where two genes were never or rarely co-mutated, and an absence of co-occurring genetic events. Further, we intersected copy number calls from our primary melanoma data with whole-genome CRISPR screening data to identify the transcription factor interferon regulatory factor 4 (IRF4) as a melanoma-associated dependency. (c) 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

引用

页码：56 / 68

页数：13

共 29 条

[21] Altered Gene Expression Patterns in Primary-versus-Metastatic Melanoma: Impact of Interactions With Stromal Cell Components
Derhovanessian, Evelyna
Mazzatti, Dawn
Pawelec, Graham
JOURNAL OF IMMUNOTHERAPY, 2008, 31 (09) : 962 - 963
[22] Low incidence of KIT gene mutations and no PDGFRA gene mutations in primary cutaneous melanoma: an immunohistochemical and molecular genetic study of Japanese cases
Terada, Tadashi
INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY, 2010, 15 (05) : 453 - 456
[23] Low incidence of KIT gene mutations and no PDGFRA gene mutations in primary cutaneous melanoma: an immunohistochemical and molecular genetic study of Japanese cases
Tadashi Terada
International Journal of Clinical Oncology, 2010, 15 : 453 - 456
[24] Genetic and genomic approaches to identify gene-gene interactions that modify severity of aganglionosis in the sox10dom model of Hirschsprung disease
Southard-Smith, E. M.
Owens, S. E.
Harris, J. T.
Walters, L. C.
Cantrell, V. A.
Bradley, K. M.
Smith, J. R.
Airey, D. C.
NEUROGASTROENTEROLOGY AND MOTILITY, 2009, 21 (02): : XXII - XXIII
[25] GENOMIC PROFILING USING CIRCULATING NUCLEIC ACIDS IN STAGE IV MELANOMA PATIENTS RECEIVING IMMUNOTHERAPY REVEALS A NOVEL GENE AMPLIFICATION LANDSCAPE AND ALLOWS FOR DETECTION OF ACTIONABLE GENE MUTATIONS
Ita, M.
Wang, J. H.
O'Leary, P.
Nolan, Y.
Toulouse, A.
Heffron, C.
Power, D.
Redmond, H. P.
BRITISH JOURNAL OF SURGERY, 2021, 108
[26] Genetic Landscape in Primary Acute Myeloid Leukemia (AML) and Relation With Wilms Tumor 1 (WT-1) Gene Expression
Gupta, Ishan
Goel, Harsh
Tanwar, Pranay
Chopra, Anita
Singh, Amar Ranjan
Meena, Jagdish Prasad
Gupta, Aditya Kumar
Viswanathan, Ganesh Kumar
Bakhshi, Sameer
Khan, Maroof Ahmad
CLINICAL LYMPHOMA MYELOMA & LEUKEMIA, 2023, 23 : S303 - S304
[27] Integrative Genomic Analyses of Patient-Matched Intracranial and Extracranial Metastases Reveal a Novel Brain-Specific Landscape of Genetic Variants in Driver Genes of Malignant Melanoma
Varaljai, Renata
Horn, Susanne
Sucker, Antje
Piercianek, Daniela
Schmitt, Verena
Carpinteiro, Alexander
Becker, Katrin Anne
Reifenberger, Julia
Roesch, Alexander
Felsberg, Joerg
Reifenberger, Guido
Sure, Ulrich
Schadendorf, Dirk
Helfrich, Iris
CANCERS, 2021, 13 (04) : 1 - 16
[28] Mouse scrapie responsive gene 1 (Scrg1): Genomic organization, physical linkage to Sap30, genetic mapping on chromosome 8, and expression in neuronal primary cell cultures
Dron, M
Tartare, X
Guillo, F
Haik, S
Barbin, G
Maury, C
Tovey, M
Dandoy-Dron, F
GENOMICS, 2000, 70 (01) : 140 - 149
[29] The Role of Genetic Polymorphisms as Related to One-Carbon Metabolism, Vitamin B6, and Gene-Nutrient Interactions in Maintaining Genomic Stability and Cell Viability in Chinese Breast Cancer Patients
Wu, Xiayu
Xu, Weijiang
Zhou, Tao
Cao, Neng
Ni, Juan
Zou, Tianning
Liang, Ziqing
Wang, Xu
Fenech, Michael
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2016, 17 (07)

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