ABCMdb

PMID: 21809164

Rittenhouse DW, Talbott VA, Anklesaria Z, Brody JR, Witkiewicz AK, Yeo CJ
Subject Review: Pancreatic Ductal Adenocarcinoma in the Setting of Mutations in the Cystic Fibrosis Transmembrane Conductance Regulator Gene: Case Report and Review of the Literature.
J Gastrointest Surg. 2011 Aug 2., 2011-08-02 [PubMed]

Sentences

No. Mutations Sentence Comment

4 ABCC7 p.Trp1282* ABCC7 p.Trp1282* Patients and Methods We report a case of a patient with PDAwho underwent resection, who is a carrier for the W1282X nonsense mutation in the CFTR gene. Login to comment 10 ABCC7 p.Trp1282* W1282X mutation Introduction Cystic fibrosis (CF) is the most common lethal autosomal recessive inherited disease amongst Caucasians.1 The gene responsible for CF is on chromosome 7 and encodes the cystic fibrosis transmembrane conductance regulator (CFTR) protein, which functions as a chloride channel regulated by cyclic AMP.2 Much work has been accomplished over the past 20 years identifying over 1,300 different mutations in the CFTR gene. Login to comment 19 ABCC7 p.Trp1282* A less common mutation in the CFTR gene is the W1282X, where a G to A base pair substitution at nucleotide 3978 leads to a substitution of a tryptophan amino acid residue with generation of a premature stop codon. Login to comment 20 ABCC7 p.Trp1282* Albeit far less common than the ΔF508 mutation, the W1282X mutation has been shown to occur with a tenfold higher frequency in patients with PDAwhen compared to controls.8 We recently operated on a patient with PDA who had a family history of CF. Login to comment 21 ABCC7 p.Trp1282* The patient underwent genetic testing and was found to harbor a heterozygous W1282X mutation in the CFTR gene. Login to comment 45 ABCC7 p.Trp1282* Genetic analysis revealed the patient to harbor a heterozygous W1282X mutation in the CFTR gene. Login to comment 56 ABCC7 p.Arg117His ABCC7 p.Trp1282* The four most prevalent genotypes were the ΔF508 mutation (n=47), 5T allele (n=44), W1282X mutation (n=6), and R117H mutation (n=5). Login to comment 57 ABCC7 p.Trp1282* The present case is the sixth W1282X mutation in the setting of PDA to have been reported in the English literature, and only the second publication to note this association. Login to comment 60 ABCC7 p.Trp1282* ABCC7 p.Trp1282* b Intraductal papillary mucinous neoplasm with mild dysplasia in the mucinous cells lining cyst wall (hematoxylin and eosin stain, ×200 original magnification) patient underwent genetic testing and was found to be heterozygous for the W1282X CFTR gene mutation. Login to comment 61 ABCC7 p.Trp1282* The W1282X mutation is a class I CFTR gene nonsense mutation that occurs with a frequency of 1% in the population and has only been reported in one publication with five other patients with PDA.8 Below, we discuss the significance of CFTR gene mutation carrier status in the risk of developing PDA and what this means in terms of cancer screening and surveillance. Login to comment 71 ABCC7 p.Trp1282* None of the patients tested in the McWilliams study had the W1282X mutation. Login to comment 84 ABCC7 p.Gly551Asp ABCC7 p.Arg117His ABCC7 p.Trp1282* ABCC7 p.Trp1282* ABCC7 p.Trp1282* ABCC7 p.Trp1282* ABCC7 p.Asn1303Lys ABCC7 p.Ser549Arg Klapman et al. suggested screening those patients that have two or more first degree relatives with PDA as Year Author Number of patients Average age (years) Pathology Genotype 2001 Malats 9 66.5 PDA 3 ΔF508 6 5T Allele 2003 Pezzilli 1 73.8 PDA 5T Allele 2003 Matsubayashi 42 Not reported PDA 6 ΔF508 36 5T Allele 2006 Piepoli 3 63 PDA 3 ΔF508 2010 Rebours 1 52 IPMN with PanIN-2 2789+G>A/5T Allele 2010 McWilliams 50 67 PDA 35 ΔF508 5 R117H 5 W1282X G551D N1303K R347 P S549R Δ1507 2011 Present Study 1 77 PDA W1282X Table 2 Patients with pancreatic tumors and heterozygous mutations in the CFTR gene CFTR cystic fibrosis transmembrane regulator, PDA pancreatic ductal adenocarcinoma, ΔF508 Delta F508, IPMN intraductal papillary mucinous neoplasm, PanIN-2 pancreatic intraepithelial neoplasia-2 well as those with a family history of any of the known hereditary pancreatic cancer syndromes such as familial adenomatous polyposis, hereditary nonpolyposis colorectal cancer syndrome, hereditary pancreatitis, hereditary breast/ ovarian cancer syndrome, Peutz-Jeghers syndrome, and familial atypical multiple mole and melanoma syndrome.24 It might be worthwhile for those patients with a family history of CF and who have other risk factors such as smoking and obesity, who are known carriers of any of the more disease-associated mutations (i.e., ΔF508, W1282X) to be screened for PDA. Login to comment 85 ABCC7 p.Trp1282* The W1282X mutation, found in our proband, is approximately 66 times less common than the ΔF508 mutation in the general population. Login to comment 88 ABCC7 p.Trp1282* The patient was found to harbor a rare nonsense mutation in the CFTR gene (W1282X) that has an increased prevalence in the Ashkenazi Jewish population. Login to comment