CDKN2A is the main susceptibility gene in Italian pancreatic cancer families

Paola Ghiorzo, Giuseppe Fornarini, Stefania Sciallero, Linda Battistuzzi, Fiorenza Belli, Loris Bernard, Luigina Bonelli, Giacomo Borgonovo, William Bruno, Franco De Cian, Andrea Decensi, Marco Filauro, Francesca Faravelli, Alberto Gozza, Sara Gargiulo, Frederique Mariette, Sabina Nasti, Lorenza Pastorino, Paola Queirolo, Vincenzo SavarinoLiliana Varesco, Giovanna Bianchi Scarrà

Research output: Contribution to journalArticle

Abstract

Background: Most familial pancreatic cancer (FPC) remains unexplained. The identification of individuals with a high genetic risk of developing pancreatic adenocarcinoma (PC) is important to elucidate its biological basis and is critical to better define emerging strategies for the detection of early pancreatic neoplasms. Patients and methods: A series of 225 consecutively enrolled patients with PC were tested for CDKN2A mutations. After personal and family cancer histories of all the patients had been reviewed, a subset of the patients were classified as FPC and were also tested for mutations in PALLD, PALB2, BRCA1 and BRCA2 as FPC candidate genes. Results: The CDKN2A mutation rate in the 225 PC cases was 5.7%. The CDKN2A founder mutations, p.E27X and p.G101W, were predominant, but the mutation spectrum also included p.L65P, p.G67R and two novel, potentially pathogenic variants, promoter variant c.-201ACTC>CTTT and p.R144C. None of the patients with FPC harboured germline mutations in PALLD, PALB2 or BRCA2. One family was positive for the BRCA1 UV variant p.P727L. Strikingly, five of 16 patients with FPC (31%) carried CDKN2A mutations. Conclusion These findings suggest that a sizeable subset of Italian FPC families may carry CDKN2A mutations. This result may be of value for identifying the best candidates for future PC screening trials in Italy.

Original languageEnglish
Pages (from-to)164-170
Number of pages7
JournalJournal of Medical Genetics
Volume49
Issue number3
DOIs
Publication statusPublished - Mar 2012

Fingerprint

Pancreatic Neoplasms
Mutation
Adenocarcinoma
Genes
Germ-Line Mutation
Neoplasm Genes
Mutation Rate
Italy
Neoplasms

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

CDKN2A is the main susceptibility gene in Italian pancreatic cancer families. / Ghiorzo, Paola; Fornarini, Giuseppe; Sciallero, Stefania; Battistuzzi, Linda; Belli, Fiorenza; Bernard, Loris; Bonelli, Luigina; Borgonovo, Giacomo; Bruno, William; De Cian, Franco; Decensi, Andrea; Filauro, Marco; Faravelli, Francesca; Gozza, Alberto; Gargiulo, Sara; Mariette, Frederique; Nasti, Sabina; Pastorino, Lorenza; Queirolo, Paola; Savarino, Vincenzo; Varesco, Liliana; Scarrà, Giovanna Bianchi.

In: Journal of Medical Genetics, Vol. 49, No. 3, 03.2012, p. 164-170.

Research output: Contribution to journalArticle

Ghiorzo, P, Fornarini, G, Sciallero, S, Battistuzzi, L, Belli, F, Bernard, L, Bonelli, L, Borgonovo, G, Bruno, W, De Cian, F, Decensi, A, Filauro, M, Faravelli, F, Gozza, A, Gargiulo, S, Mariette, F, Nasti, S, Pastorino, L, Queirolo, P, Savarino, V, Varesco, L & Scarrà, GB 2012, 'CDKN2A is the main susceptibility gene in Italian pancreatic cancer families', Journal of Medical Genetics, vol. 49, no. 3, pp. 164-170. https://doi.org/10.1136/jmedgenet-2011-100281
Ghiorzo, Paola ; Fornarini, Giuseppe ; Sciallero, Stefania ; Battistuzzi, Linda ; Belli, Fiorenza ; Bernard, Loris ; Bonelli, Luigina ; Borgonovo, Giacomo ; Bruno, William ; De Cian, Franco ; Decensi, Andrea ; Filauro, Marco ; Faravelli, Francesca ; Gozza, Alberto ; Gargiulo, Sara ; Mariette, Frederique ; Nasti, Sabina ; Pastorino, Lorenza ; Queirolo, Paola ; Savarino, Vincenzo ; Varesco, Liliana ; Scarrà, Giovanna Bianchi. / CDKN2A is the main susceptibility gene in Italian pancreatic cancer families. In: Journal of Medical Genetics. 2012 ; Vol. 49, No. 3. pp. 164-170.
@article{da994eeb4c8c46fd8100040f2e3ae145,
title = "CDKN2A is the main susceptibility gene in Italian pancreatic cancer families",
abstract = "Background: Most familial pancreatic cancer (FPC) remains unexplained. The identification of individuals with a high genetic risk of developing pancreatic adenocarcinoma (PC) is important to elucidate its biological basis and is critical to better define emerging strategies for the detection of early pancreatic neoplasms. Patients and methods: A series of 225 consecutively enrolled patients with PC were tested for CDKN2A mutations. After personal and family cancer histories of all the patients had been reviewed, a subset of the patients were classified as FPC and were also tested for mutations in PALLD, PALB2, BRCA1 and BRCA2 as FPC candidate genes. Results: The CDKN2A mutation rate in the 225 PC cases was 5.7{\%}. The CDKN2A founder mutations, p.E27X and p.G101W, were predominant, but the mutation spectrum also included p.L65P, p.G67R and two novel, potentially pathogenic variants, promoter variant c.-201ACTC>CTTT and p.R144C. None of the patients with FPC harboured germline mutations in PALLD, PALB2 or BRCA2. One family was positive for the BRCA1 UV variant p.P727L. Strikingly, five of 16 patients with FPC (31{\%}) carried CDKN2A mutations. Conclusion These findings suggest that a sizeable subset of Italian FPC families may carry CDKN2A mutations. This result may be of value for identifying the best candidates for future PC screening trials in Italy.",
author = "Paola Ghiorzo and Giuseppe Fornarini and Stefania Sciallero and Linda Battistuzzi and Fiorenza Belli and Loris Bernard and Luigina Bonelli and Giacomo Borgonovo and William Bruno and {De Cian}, Franco and Andrea Decensi and Marco Filauro and Francesca Faravelli and Alberto Gozza and Sara Gargiulo and Frederique Mariette and Sabina Nasti and Lorenza Pastorino and Paola Queirolo and Vincenzo Savarino and Liliana Varesco and Scarr{\`a}, {Giovanna Bianchi}",
year = "2012",
month = "3",
doi = "10.1136/jmedgenet-2011-100281",
language = "English",
volume = "49",
pages = "164--170",
journal = "Journal of Medical Genetics",
issn = "0022-2593",
publisher = "BMJ Publishing Group",
number = "3",

}

TY - JOUR

T1 - CDKN2A is the main susceptibility gene in Italian pancreatic cancer families

AU - Ghiorzo, Paola

AU - Fornarini, Giuseppe

AU - Sciallero, Stefania

AU - Battistuzzi, Linda

AU - Belli, Fiorenza

AU - Bernard, Loris

AU - Bonelli, Luigina

AU - Borgonovo, Giacomo

AU - Bruno, William

AU - De Cian, Franco

AU - Decensi, Andrea

AU - Filauro, Marco

AU - Faravelli, Francesca

AU - Gozza, Alberto

AU - Gargiulo, Sara

AU - Mariette, Frederique

AU - Nasti, Sabina

AU - Pastorino, Lorenza

AU - Queirolo, Paola

AU - Savarino, Vincenzo

AU - Varesco, Liliana

AU - Scarrà, Giovanna Bianchi

PY - 2012/3

Y1 - 2012/3

N2 - Background: Most familial pancreatic cancer (FPC) remains unexplained. The identification of individuals with a high genetic risk of developing pancreatic adenocarcinoma (PC) is important to elucidate its biological basis and is critical to better define emerging strategies for the detection of early pancreatic neoplasms. Patients and methods: A series of 225 consecutively enrolled patients with PC were tested for CDKN2A mutations. After personal and family cancer histories of all the patients had been reviewed, a subset of the patients were classified as FPC and were also tested for mutations in PALLD, PALB2, BRCA1 and BRCA2 as FPC candidate genes. Results: The CDKN2A mutation rate in the 225 PC cases was 5.7%. The CDKN2A founder mutations, p.E27X and p.G101W, were predominant, but the mutation spectrum also included p.L65P, p.G67R and two novel, potentially pathogenic variants, promoter variant c.-201ACTC>CTTT and p.R144C. None of the patients with FPC harboured germline mutations in PALLD, PALB2 or BRCA2. One family was positive for the BRCA1 UV variant p.P727L. Strikingly, five of 16 patients with FPC (31%) carried CDKN2A mutations. Conclusion These findings suggest that a sizeable subset of Italian FPC families may carry CDKN2A mutations. This result may be of value for identifying the best candidates for future PC screening trials in Italy.

AB - Background: Most familial pancreatic cancer (FPC) remains unexplained. The identification of individuals with a high genetic risk of developing pancreatic adenocarcinoma (PC) is important to elucidate its biological basis and is critical to better define emerging strategies for the detection of early pancreatic neoplasms. Patients and methods: A series of 225 consecutively enrolled patients with PC were tested for CDKN2A mutations. After personal and family cancer histories of all the patients had been reviewed, a subset of the patients were classified as FPC and were also tested for mutations in PALLD, PALB2, BRCA1 and BRCA2 as FPC candidate genes. Results: The CDKN2A mutation rate in the 225 PC cases was 5.7%. The CDKN2A founder mutations, p.E27X and p.G101W, were predominant, but the mutation spectrum also included p.L65P, p.G67R and two novel, potentially pathogenic variants, promoter variant c.-201ACTC>CTTT and p.R144C. None of the patients with FPC harboured germline mutations in PALLD, PALB2 or BRCA2. One family was positive for the BRCA1 UV variant p.P727L. Strikingly, five of 16 patients with FPC (31%) carried CDKN2A mutations. Conclusion These findings suggest that a sizeable subset of Italian FPC families may carry CDKN2A mutations. This result may be of value for identifying the best candidates for future PC screening trials in Italy.

UR - http://www.scopus.com/inward/record.url?scp=84860282103&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84860282103&partnerID=8YFLogxK

U2 - 10.1136/jmedgenet-2011-100281

DO - 10.1136/jmedgenet-2011-100281

M3 - Article

C2 - 22368299

AN - SCOPUS:84860282103

VL - 49

SP - 164

EP - 170

JO - Journal of Medical Genetics

JF - Journal of Medical Genetics

SN - 0022-2593

IS - 3

ER -