Dissecting the Mutational Landscape of Cutaneous Melanoma: An Omic Analysis Based on Patients from Greece

Overview

Journal Cancers (Basel)

Publisher MDPI

Specialty Oncology

Date 2018 Mar 30

PMID 29596374

Citations 7

Authors

Georgia Kontogianni

Georgia Piroti

Ilias Maglogiannis

Aristotelis Chatziioannou

Olga Papadodima

Affiliations

Soon will be listed here.

Abstract

Melanoma is a lethal type of skin cancer, unless it is diagnosed early. Formalin-fixed, paraffin-embedded (FFPE) tissue is a valuable source for molecular assays after diagnostic examination, but isolated nucleic acids often suffer from degradation. Here, for the first time, we examine primary melanomas from Greek patients, using whole exome sequencing, so as to derive their mutational profile. Application of a bioinformatic framework revealed a total of 10,030 somatic mutations. Regarding the genes containing putative protein-altering mutations, 73 were common in at least three patients. Sixty-five of these 73 top common genes have been previously identified in melanoma cases. Biological processes related to melanoma were affected by varied genes in each patient, suggesting differences in the components of a pathway possibly contributing to pathogenesis. We performed a multi-level analysis highlighting a short list of candidate genes with a probable causative role in melanoma.

Citing Articles

Assessment of tumoral and peritumoral inflammatory reaction in cutaneous malignant melanomas.

Fruntelata R, Bakri A, Stoica G, Mogoanta L, Ionovici N, Popescu G Rom J Morphol Embryol. 2023; 64(1):41-48.

PMID: 37128790 PMC: 10257785. DOI: 10.47162/RJME.64.1.05.

Melanoma Cellular Signaling Transduction Pathways Targeted by Polyphenols Action Mechanisms.

Isacescu E, Chiroi P, Zanoaga O, Nutu A, Budisan L, Pirlog R Antioxidants (Basel). 2023; 12(2).

PMID: 36829966 PMC: 9952468. DOI: 10.3390/antiox12020407.

A Comprehensive Analysis of Cutaneous Melanoma Patients in Greece Based on Multi-Omic Data.

Kontogianni G, Voutetakis K, Piroti G, Kypreou K, Stefanaki I, Vlachavas E Cancers (Basel). 2023; 15(3).

PMID: 36765773 PMC: 9913631. DOI: 10.3390/cancers15030815.

UV-Induced Somatic Mutations Driving Clonal Evolution in Healthy Skin, Nevus, and Cutaneous Melanoma.

Loras A, Gil-Barrachina M, Marques-Torrejon M, Perez-Pastor G, Martinez-Cadenas C Life (Basel). 2022; 12(9).

PMID: 36143375 PMC: 9503451. DOI: 10.3390/life12091339.

Non-BRAF Mutant Melanoma: Molecular Features and Therapeutical Implications.

Vanni I, Tanda E, Dalmasso B, Pastorino L, Andreotti V, Bruno W Front Mol Biosci. 2020; 7:172.

PMID: 32850962 PMC: 7396525. DOI: 10.3389/fmolb.2020.00172.

References

Kypreou K, Stefanaki I, Antonopoulou K, Karagianni F, Ntritsos G, Zaras A . Prediction of Melanoma Risk in a Southern European Population Based on a Weighted Genetic Risk Score. J Invest Dermatol. 2016; 136(3):690-695. DOI: 10.1016/j.jid.2015.12.007. View

Liu X, Jian X, Boerwinkle E . dbNSFP v2.0: a database of human non-synonymous SNVs and their functional predictions and annotations. Hum Mutat. 2013; 34(9):E2393-402. PMC: 4109890. DOI: 10.1002/humu.22376. View

Sturm R, Duffy D, Zhao Z, Leite F, Stark M, Hayward N . A single SNP in an evolutionary conserved region within intron 86 of the HERC2 gene determines human blue-brown eye color. Am J Hum Genet. 2008; 82(2):424-31. PMC: 2427173. DOI: 10.1016/j.ajhg.2007.11.005. View

Forbes S, Beare D, Gunasekaran P, Leung K, Bindal N, Boutselakis H . COSMIC: exploring the world's knowledge of somatic mutations in human cancer. Nucleic Acids Res. 2014; 43(Database issue):D805-11. PMC: 4383913. DOI: 10.1093/nar/gku1075. View

Majewski J, Schwartzentruber J, Lalonde E, Montpetit A, Jabado N . What can exome sequencing do for you?. J Med Genet. 2011; 48(9):580-9. DOI: 10.1136/jmedgenet-2011-100223. View

Gonzalez-Perez A, Lopez-Bigas N . Functional impact bias reveals cancer drivers. Nucleic Acids Res. 2012; 40(21):e169. PMC: 3505979. DOI: 10.1093/nar/gks743. View

Dutton-Regester K, Hayward N . Reviewing the somatic genetics of melanoma: from current to future analytical approaches. Pigment Cell Melanoma Res. 2012; 25(2):144-54. DOI: 10.1111/j.1755-148X.2012.00975.x. View

Van Allen E, Wagle N, Stojanov P, Perrin D, Cibulskis K, Marlow S . Whole-exome sequencing and clinical interpretation of formalin-fixed, paraffin-embedded tumor samples to guide precision cancer medicine. Nat Med. 2014; 20(6):682-8. PMC: 4048335. DOI: 10.1038/nm.3559. View

Zhang T, Dutton-Regester K, Brown K, Hayward N . The genomic landscape of cutaneous melanoma. Pigment Cell Melanoma Res. 2016; 29(3):266-83. DOI: 10.1111/pcmr.12459. View

10.

Walia V, Mu E, Lin J, Samuels Y . Delving into somatic variation in sporadic melanoma. Pigment Cell Melanoma Res. 2012; 25(2):155-70. PMC: 3374856. DOI: 10.1111/j.1755-148X.2012.00976.x. View

11.

Spencer D, Sehn J, Abel H, Watson M, Pfeifer J, Duncavage E . Comparison of clinical targeted next-generation sequence data from formalin-fixed and fresh-frozen tissue specimens. J Mol Diagn. 2013; 15(5):623-33. PMC: 4912568. DOI: 10.1016/j.jmoldx.2013.05.004. View

12.

Aoude L, Wadt K, Pritchard A, Hayward N . Genetics of familial melanoma: 20 years after CDKN2A. Pigment Cell Melanoma Res. 2014; 28(2):148-60. DOI: 10.1111/pcmr.12333. View

13.

Choucair K, Guerard K, Ejdelman J, Chevalier S, Yoshimoto M, Scarlata E . The 16p13.3 (PDPK1) Genomic Gain in Prostate Cancer: A Potential Role in Disease Progression. Transl Oncol. 2013; 5(6):453-60. PMC: 3568696. DOI: 10.1593/tlo.12286. View

14.

Nikolaev S, Rimoldi D, Iseli C, Valsesia A, Robyr D, Gehrig C . Exome sequencing identifies recurrent somatic MAP2K1 and MAP2K2 mutations in melanoma. Nat Genet. 2011; 44(2):133-9. DOI: 10.1038/ng.1026. View

15.

Wang Y, Marino-Enriquez A, Bennett R, Zhu M, Shen Y, Eilers G . Dystrophin is a tumor suppressor in human cancers with myogenic programs. Nat Genet. 2014; 46(6):601-6. PMC: 4225780. DOI: 10.1038/ng.2974. View

16.

Chatzinasiou F, Lill C, Kypreou K, Stefanaki I, Nicolaou V, Spyrou G . Comprehensive field synopsis and systematic meta-analyses of genetic association studies in cutaneous melanoma. J Natl Cancer Inst. 2011; 103(16):1227-35. PMC: 4719704. DOI: 10.1093/jnci/djr219. View

17.

Aitken J, Welch J, Duffy D, Milligan A, Green A, Martin N . CDKN2A variants in a population-based sample of Queensland families with melanoma. J Natl Cancer Inst. 1999; 91(5):446-52. DOI: 10.1093/jnci/91.5.446. View

18.

Raphael B, Dobson J, Oesper L, Vandin F . Identifying driver mutations in sequenced cancer genomes: computational approaches to enable precision medicine. Genome Med. 2014; 6(1):5. PMC: 3978567. DOI: 10.1186/gm524. View

19.

Gagliardi P, Puliafito A, Primo L . PDK1: At the crossroad of cancer signaling pathways. Semin Cancer Biol. 2017; 48:27-35. DOI: 10.1016/j.semcancer.2017.04.014. View

20.

Antonopoulou K, Stefanaki I, Lill C, Chatzinasiou F, Kypreou K, Karagianni F . Updated field synopsis and systematic meta-analyses of genetic association studies in cutaneous melanoma: the MelGene database. J Invest Dermatol. 2014; 135(4):1074-1079. DOI: 10.1038/jid.2014.491. View