Factors predicting the occurrence of germline mutations in candidate genes among patients with cutaneous malignant melanoma from South Italy

Milena Casula, Maria Colombino, Maria P. Satta, Antonio Cossu, Amelia Lissia, Mario Budroni, Ester Simeone, Rosa Calemma, Cinzia Loddo, Corrado Caracò, Nicola Mozzillo, Antonio Daponte, Giuseppe Comella, Sergio Canzanella, Michele Guida, Giuseppe Castello, Paolo A. Ascierto, Giuseppe Palmieri

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Clinical predictors for germline mutations of candidate genes in large clinic based population of patients with cutaneous malignant melanoma (CMM) are widely awaited. Using denaturing high-performance liquid chromatography (DHPLC) analysis and DNA sequencing, 557 consecutively-collected CMM patients originating from South Italy were screened for CDKN2A germline mutations; subsets of them were screened for mutations in the BRAF and BRCA2 genes. Seven CDKN2A mutations were detected in 14 (2.5%) CMM patients. Relative risk of carrying a CDKN2A mutation for CMM patients was demonstrated to significantly increase with the presence of familial recurrence of melanoma (risk ratio (RR) = 6.31; p = 0.0009), multiple primary melanomas (RR = 3.43; p = 0.0014), and early onset age (RR = 4.56; p = 0.0026). All CDKN2A mutations were observed in non-Sardinian patients (14/441; 3.2%), whereas BRAF and BRCA2 genes were found mutated in Sardinian patients (3/116; 2.6%). Such indicators of the presence of CDKN2A mutations will be useful in counselling patients about undergoing genetic testing. Our findings strongly suggest that mutation rates of candidate cancer genes may deeply vary among CMM patients from different geographical areas.

Original languageEnglish
Pages (from-to)137-143
Number of pages7
JournalEuropean Journal of Cancer
Volume43
Issue number1
DOIs
Publication statusPublished - Jan 2007

Fingerprint

Germ-Line Mutation
Italy
Genes
Mutation
BRCA2 Gene
Odds Ratio
Cutaneous Malignant Melanoma
Neoplasm Genes
Genetic Testing
Mutation Rate
DNA Sequence Analysis
Age of Onset
Counseling
Melanoma
High Pressure Liquid Chromatography
Recurrence

Keywords

  • Cancer genes
  • Genetic testing
  • Mutation analysis
  • Polymerase chain reaction

ASJC Scopus subject areas

  • Cancer Research
  • Hematology
  • Oncology

Cite this

Factors predicting the occurrence of germline mutations in candidate genes among patients with cutaneous malignant melanoma from South Italy. / Casula, Milena; Colombino, Maria; Satta, Maria P.; Cossu, Antonio; Lissia, Amelia; Budroni, Mario; Simeone, Ester; Calemma, Rosa; Loddo, Cinzia; Caracò, Corrado; Mozzillo, Nicola; Daponte, Antonio; Comella, Giuseppe; Canzanella, Sergio; Guida, Michele; Castello, Giuseppe; Ascierto, Paolo A.; Palmieri, Giuseppe.

In: European Journal of Cancer, Vol. 43, No. 1, 01.2007, p. 137-143.

Research output: Contribution to journalArticle

Casula, Milena ; Colombino, Maria ; Satta, Maria P. ; Cossu, Antonio ; Lissia, Amelia ; Budroni, Mario ; Simeone, Ester ; Calemma, Rosa ; Loddo, Cinzia ; Caracò, Corrado ; Mozzillo, Nicola ; Daponte, Antonio ; Comella, Giuseppe ; Canzanella, Sergio ; Guida, Michele ; Castello, Giuseppe ; Ascierto, Paolo A. ; Palmieri, Giuseppe. / Factors predicting the occurrence of germline mutations in candidate genes among patients with cutaneous malignant melanoma from South Italy. In: European Journal of Cancer. 2007 ; Vol. 43, No. 1. pp. 137-143.
@article{6548c30df93f4d9e938e2059321869a5,
title = "Factors predicting the occurrence of germline mutations in candidate genes among patients with cutaneous malignant melanoma from South Italy",
abstract = "Clinical predictors for germline mutations of candidate genes in large clinic based population of patients with cutaneous malignant melanoma (CMM) are widely awaited. Using denaturing high-performance liquid chromatography (DHPLC) analysis and DNA sequencing, 557 consecutively-collected CMM patients originating from South Italy were screened for CDKN2A germline mutations; subsets of them were screened for mutations in the BRAF and BRCA2 genes. Seven CDKN2A mutations were detected in 14 (2.5{\%}) CMM patients. Relative risk of carrying a CDKN2A mutation for CMM patients was demonstrated to significantly increase with the presence of familial recurrence of melanoma (risk ratio (RR) = 6.31; p = 0.0009), multiple primary melanomas (RR = 3.43; p = 0.0014), and early onset age (RR = 4.56; p = 0.0026). All CDKN2A mutations were observed in non-Sardinian patients (14/441; 3.2{\%}), whereas BRAF and BRCA2 genes were found mutated in Sardinian patients (3/116; 2.6{\%}). Such indicators of the presence of CDKN2A mutations will be useful in counselling patients about undergoing genetic testing. Our findings strongly suggest that mutation rates of candidate cancer genes may deeply vary among CMM patients from different geographical areas.",
keywords = "Cancer genes, Genetic testing, Mutation analysis, Polymerase chain reaction",
author = "Milena Casula and Maria Colombino and Satta, {Maria P.} and Antonio Cossu and Amelia Lissia and Mario Budroni and Ester Simeone and Rosa Calemma and Cinzia Loddo and Corrado Carac{\`o} and Nicola Mozzillo and Antonio Daponte and Giuseppe Comella and Sergio Canzanella and Michele Guida and Giuseppe Castello and Ascierto, {Paolo A.} and Giuseppe Palmieri",
year = "2007",
month = "1",
doi = "10.1016/j.ejca.2006.07.017",
language = "English",
volume = "43",
pages = "137--143",
journal = "European Journal of Cancer",
issn = "0959-8049",
publisher = "Elsevier Ltd",
number = "1",

}

TY - JOUR

T1 - Factors predicting the occurrence of germline mutations in candidate genes among patients with cutaneous malignant melanoma from South Italy

AU - Casula, Milena

AU - Colombino, Maria

AU - Satta, Maria P.

AU - Cossu, Antonio

AU - Lissia, Amelia

AU - Budroni, Mario

AU - Simeone, Ester

AU - Calemma, Rosa

AU - Loddo, Cinzia

AU - Caracò, Corrado

AU - Mozzillo, Nicola

AU - Daponte, Antonio

AU - Comella, Giuseppe

AU - Canzanella, Sergio

AU - Guida, Michele

AU - Castello, Giuseppe

AU - Ascierto, Paolo A.

AU - Palmieri, Giuseppe

PY - 2007/1

Y1 - 2007/1

N2 - Clinical predictors for germline mutations of candidate genes in large clinic based population of patients with cutaneous malignant melanoma (CMM) are widely awaited. Using denaturing high-performance liquid chromatography (DHPLC) analysis and DNA sequencing, 557 consecutively-collected CMM patients originating from South Italy were screened for CDKN2A germline mutations; subsets of them were screened for mutations in the BRAF and BRCA2 genes. Seven CDKN2A mutations were detected in 14 (2.5%) CMM patients. Relative risk of carrying a CDKN2A mutation for CMM patients was demonstrated to significantly increase with the presence of familial recurrence of melanoma (risk ratio (RR) = 6.31; p = 0.0009), multiple primary melanomas (RR = 3.43; p = 0.0014), and early onset age (RR = 4.56; p = 0.0026). All CDKN2A mutations were observed in non-Sardinian patients (14/441; 3.2%), whereas BRAF and BRCA2 genes were found mutated in Sardinian patients (3/116; 2.6%). Such indicators of the presence of CDKN2A mutations will be useful in counselling patients about undergoing genetic testing. Our findings strongly suggest that mutation rates of candidate cancer genes may deeply vary among CMM patients from different geographical areas.

AB - Clinical predictors for germline mutations of candidate genes in large clinic based population of patients with cutaneous malignant melanoma (CMM) are widely awaited. Using denaturing high-performance liquid chromatography (DHPLC) analysis and DNA sequencing, 557 consecutively-collected CMM patients originating from South Italy were screened for CDKN2A germline mutations; subsets of them were screened for mutations in the BRAF and BRCA2 genes. Seven CDKN2A mutations were detected in 14 (2.5%) CMM patients. Relative risk of carrying a CDKN2A mutation for CMM patients was demonstrated to significantly increase with the presence of familial recurrence of melanoma (risk ratio (RR) = 6.31; p = 0.0009), multiple primary melanomas (RR = 3.43; p = 0.0014), and early onset age (RR = 4.56; p = 0.0026). All CDKN2A mutations were observed in non-Sardinian patients (14/441; 3.2%), whereas BRAF and BRCA2 genes were found mutated in Sardinian patients (3/116; 2.6%). Such indicators of the presence of CDKN2A mutations will be useful in counselling patients about undergoing genetic testing. Our findings strongly suggest that mutation rates of candidate cancer genes may deeply vary among CMM patients from different geographical areas.

KW - Cancer genes

KW - Genetic testing

KW - Mutation analysis

KW - Polymerase chain reaction

UR - http://www.scopus.com/inward/record.url?scp=33846127796&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33846127796&partnerID=8YFLogxK

U2 - 10.1016/j.ejca.2006.07.017

DO - 10.1016/j.ejca.2006.07.017

M3 - Article

VL - 43

SP - 137

EP - 143

JO - European Journal of Cancer

JF - European Journal of Cancer

SN - 0959-8049

IS - 1

ER -