PMID- 29492214
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220408
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 9
IP  - 9
DP  - 2018 Feb 2
TI  - Genetic alterations in main candidate genes during melanoma progression.
PG  - 8531-8541
LID - 10.18632/oncotarget.23989 [doi]
AB  - Cutaneous melanoma is a common and aggressive human skin cancers. Much is 
      actually known about the molecular mechanisms underlying melanoma pathogenesis. 
      The aim of the study was to evaluate any possible correlation between mutations 
      in main growth-controlling genes (BRAF, NRAS, CDKN2A) and copy number variations 
      in frequently amplified candidate genes (MITF, EGFR, CCND1, cMET, and cKIT) 
      during melanoma initiation and progression. A large series of primary and 
      secondary melanoma tissue samples (N = 274) from 232 consecutively-collected 
      patients of Italian origin as well as 32 tumor cell lines derived from primary 
      and metastatic melanomas underwent mutation screening and fluorescence in situ 
      hybridization (FISH) analysis. Overall, BRAF, NRAS, and CDKN2A were found mutated 
      in 62.5%, 12.5% and 59% cell lines and in 47%, 16%, 12% tumor tissues, 
      respectively. Quite identical mutation patterns between primary tumors and 
      metastatic lesions were found for BRAF and NRAS genes; mutations of CDKN2A gene 
      appeared to be instead selected during tumor progression. In cell lines, high 
      rates of gene amplifications were observed (varying from 12.5% for cKIT to 50% 
      for MITF); vast majority of cell lines (75%) presented at least one amplified 
      gene. Conversely, prevalence of gene amplification was significantly and 
      progressively decreasing in melanoma metastases (12%) and primary melanomas (4%). 
      Our findings suggest that gene amplifications may be acquired during the late 
      phases of melanoma evolution and mostly act as "passenger" or "non-causative" 
      alterations.
FAU - Sini, Maria Cristina
AU  - Sini MC
AD  - Unit of Cancer Genetics, Institute of Biomolecular Chemistry, National Research 
      Council, Sassari, Italy.
FAU - Doneddu, Valentina
AU  - Doneddu V
AD  - Department of Surgical, Microsurgical and Medical Sciences, University of 
      Sassari, Sassari, Italy.
FAU - Paliogiannis, Panagiotis
AU  - Paliogiannis P
AD  - Department of Clinical and Experimental Medicine, University of Sassari, Sassari, 
      Italy.
FAU - Casula, Milena
AU  - Casula M
AD  - Unit of Cancer Genetics, Institute of Biomolecular Chemistry, National Research 
      Council, Sassari, Italy.
FAU - Colombino, Maria
AU  - Colombino M
AD  - Unit of Cancer Genetics, Institute of Biomolecular Chemistry, National Research 
      Council, Sassari, Italy.
FAU - Manca, Antonella
AU  - Manca A
AD  - Unit of Cancer Genetics, Institute of Biomolecular Chemistry, National Research 
      Council, Sassari, Italy.
FAU - Botti, Gerardo
AU  - Botti G
AD  - Istituto Nazionale Tumori, Fondazione Pascale, Napoli, Italy.
FAU - Ascierto, Paolo A
AU  - Ascierto PA
AD  - Istituto Nazionale Tumori, Fondazione Pascale, Napoli, Italy.
FAU - Lissia, Amelia
AU  - Lissia A
AD  - Department of Surgical, Microsurgical and Medical Sciences, University of 
      Sassari, Sassari, Italy.
FAU - Cossu, Antonio
AU  - Cossu A
AD  - Department of Surgical, Microsurgical and Medical Sciences, University of 
      Sassari, Sassari, Italy.
FAU - Palmieri, Giuseppe
AU  - Palmieri G
AD  - Unit of Cancer Genetics, Institute of Biomolecular Chemistry, National Research 
      Council, Sassari, Italy.
LA  - eng
PT  - Journal Article
DEP - 20180103
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
PMC - PMC5823576
OTO - NOTNLM
OT  - fluorescence in situ hybridization (FISH) analysis
OT  - genetic heterogeneity
OT  - malignant melanoma
OT  - mutation analysis
OT  - oncogenic driver genes
COIS- CONFLICTS OF INTEREST Paolo A. Ascierto has/had consultant and advisory role for 
      Bristol Myers Squibb, Merck Sharp & Dohme, Roche-Genenetech, Novartis, Ventana 
      Medical Systems, Inc, and Amgen. He received research fund from Bristol Myers 
      Squibb, Roche-Genetech, and Ventana. All the remaining authors declare the 
      absence of any conflicts of interest.
EDAT- 2018/03/02 06:00
MHDA- 2018/03/02 06:01
PMCR- 2018/02/02
CRDT- 2018/03/02 06:00
PHST- 2017/03/02 00:00 [received]
PHST- 2017/11/13 00:00 [accepted]
PHST- 2018/03/02 06:00 [entrez]
PHST- 2018/03/02 06:00 [pubmed]
PHST- 2018/03/02 06:01 [medline]
PHST- 2018/02/02 00:00 [pmc-release]
AID - 23989 [pii]
AID - 10.18632/oncotarget.23989 [doi]
PST - epublish
SO  - Oncotarget. 2018 Jan 3;9(9):8531-8541. doi: 10.18632/oncotarget.23989. 
      eCollection 2018 Feb 2.