No Tissue Expression of KRAS or BRAF Mutations in 61 Adult Patients Treated for Esophageal Atresia in Early Childhood

Kien Xuan Dang; Tho Ho; Saara Sistonen; Antti Koivusalo; Mikko Pakarinen; Risto Rintala; Ulf-Hakan Stenman; Arto Orpana; Jakob Stenman

doi:10.1055/s-0037-1605346

European Journal of Pediatric Surgery, Inhaltsverzeichnis

Eur J Pediatr Surg 2018; 28(05): 413-419
DOI: 10.1055/s-0037-1605346

Original Article

Georg Thieme Verlag KG Stuttgart · New York

No Tissue Expression of KRAS or BRAF Mutations in 61 Adult Patients Treated for Esophageal Atresia in Early Childhood

Kien Xuan Dang

¹Minerva Foundation Institute for Medical Research, Helsinki, Finland

,

Tho Ho

²Department of Genomics, BPARC, Vietnam Military Medical University, Vietnam

,

Saara Sistonen

³Department of Pediatric Surgery, Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland

,

Antti Koivusalo

³Department of Pediatric Surgery, Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland

,

Mikko Pakarinen

³Department of Pediatric Surgery, Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland

,

Risto Rintala

³Department of Pediatric Surgery, Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland

,

Ulf-Hakan Stenman

⁴Department of Clinical Chemistry, University of Helsinki, Helsinki, Finland

,

Arto Orpana

⁵Laboratory of Genetics, HUSLAB, Helsinki University Central Hospital, Helsinki, Finland

,

Jakob Stenman

⁶Institute for Molecular Medicine, Finland, Helsinki, Finland

⁷Department for Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden

› Institutsangaben

Abstract

Background Previous studies have reported an association among esophageal atresia (EA), Barrett's esophagus, and esophageal adenocarcinoma later in life.

Objective The objective of the article is to evaluate KRAS and BRAF mutations as potential genetic markers for early detection of malignant transformation, we used an ultrasensitive technique to detect tissue expression of KRAS and BRAF mutations in endoscopic biopsies from 61 adult patients under follow-up after treatment for EA.

Materials and Methods RNA was extracted from 112 fresh-frozen endoscopic tissue biopsies from 61 adult patients treated for EA in early childhood. RNA was reverse transcribed using the extendable blocking probe reverse transcription method. KRAS codons 12 and 13, as well as BRAF mutations were detected by quantitative polymerase chain reaction.

Results No mutations of KRAS codon 12, KRAS codon 13, or BRAF were found in 112 endoscopic biopsy samples from 61 patients.

Conclusion Despite the presence of histological findings indicating long-standing gastroesophageal reflux in 25%, as well as symptomatic gastroesophageal reflux in more than 40%, there was no detectable tissue expression of KRAS or BRAF mutations in this cohort of patients.

Keywords

esophageal atresia - extendable blocking probe - KRAS - BRAF

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Referenzen

References
1 Spitz L. Oesophageal atresia. Orphanet J Rare Dis 2007; 2: 24
2 Depaepe A, Dolk H, Lechat MF. ; EUROCAT Working Group. The epidemiology of tracheo-oesophageal fistula and oesophageal atresia in Europe. Arch Dis Child 1993; 68 (06) 743-748
3 Torfs CP, Curry CJ, Bateson TF. Population-based study of tracheoesophageal fistula and esophageal atresia. Teratology 1995; 52 (04) 220-232
4 Holland AJ, Fitzgerald DA. Oesophageal atresia and tracheo-oesophageal fistula: current management strategies and complications. Paediatr Respir Rev 2010; 11 (02) 100-106
5 Krug E, Bergmeijer JH, Dees J, de Krijger R, Mooi WJ, Hazebroek FW. Gastroesophageal reflux and Barrett's esophagus in adults born with esophageal atresia. Am J Gastroenterol 1999; 94 (10) 2825-2828
6 Koivusalo A, Pakarinen MP, Rintala RJ. The cumulative incidence of significant gastrooesophageal reflux in patients with oesophageal atresia with a distal fistula--a systematic clinical, pH-metric, and endoscopic follow-up study. J Pediatr Surg 2007; 42 (02) 370-374
7 Sistonen SJ, Koivusalo A, Nieminen U. , et al. Esophageal morbidity and function in adults with repaired esophageal atresia with tracheoesophageal fistula: a population-based long-term follow-up. Ann Surg 2010; 251 (06) 1167-1173
8 Maltby EL, Dyson MJ, Wheeler MR, Thomson M, Sethuraman C, Cohen MC. Molecular abnormalities in pediatric barrett esophagus: can we test for potential of neoplastic progression?. Pediatr Dev Pathol 2010; 13 (04) 310-317
9 Shaheen NJ, Richter JE. Barrett's oesophagus. Lancet 2009; 373 (9666): 850-861
10 Koppert LB, Wijnhoven BP, van Dekken H, Tilanus HW, Dinjens WN. The molecular biology of esophageal adenocarcinoma. J Surg Oncol 2005; 92 (03) 169-190
11 Rintala RJ, Sistonen S, Pakarinen MP. Outcome of esophageal atresia beyond childhood. Semin Pediatr Surg 2009; 18 (01) 50-56
12 Vergouwe FW, IJsselstijn H, Wijnen RM, Bruno MJ, Spaander MC. Screening and surveillance in esophageal atresia patients: current knowledge and future perspectives. Eur J Pediatr Surg 2015; 25 (04) 345-352
13 Deurloo JA, van Lanschot JJ, Drillenburg P, Aronson DC. Esophageal squamous cell carcinoma 38 years after primary repair of esophageal atresia. J Pediatr Surg 2001; 36 (04) 629-630
14 Jayasekera CS, Desmond PV, Holmes JA, Kitson M, Taylor AC. Cluster of 4 cases of esophageal squamous cell cancer developing in adults with surgically corrected esophageal atresia--time for screening to start. J Pediatr Surg 2012; 47 (04) 646-651
15 Adzick NS, Fisher JH, Winter HS, Sandler RH, Hendren WH. Esophageal adenocarcinoma 20 years after esophageal atresia repair. J Pediatr Surg 1989; 24 (08) 741-744
16 Alfaro L, Bermas H, Fenoglio M, Parker R, Janik JS. Are patients who have had a tracheoesophageal fistula repair during infancy at risk for esophageal adenocarcinoma during adulthood?. J Pediatr Surg 2005; 40 (04) 719-720
17 Pultrum BB, Bijleveld CM, de Langen ZJ, Plukker JT. Development of an adenocarcinoma of the esophagus 22 years after primary repair of a congenital atresia. J Pediatr Surg 2005; 40 (12) e1-e4
18 Sistonen SJ, Koivusalo A, Lindahl H, Pukkala E, Rintala RJ, Pakarinen MP. Cancer after repair of esophageal atresia: population-based long-term follow-up. J Pediatr Surg 2008; 43 (04) 602-605
19 Davies H, Bignell GR, Cox C. , et al. Mutations of the BRAF gene in human cancer. Nature 2002; 417 (6892): 949-954
20 Cantwell-Dorris ER, O'Leary JJ, Sheils OM. BRAFV600E: implications for carcinogenesis and molecular therapy. Mol Cancer Ther 2011; 10 (03) 385-394
21 Samatar AA, Poulikakos PI. Targeting RAS-ERK signalling in cancer: promises and challenges. Nat Rev Drug Discov 2014; 13 (12) 928-942
22 Vakiani E, Solit DB. KRAS and BRAF: drug targets and predictive biomarkers. J Pathol 2011; 223 (02) 219-229
23 Lord RV, O'Grady R, Sheehan C, Field AF, Ward RL. K-ras codon 12 mutations in Barrett's oesophagus and adenocarcinomas of the oesophagus and oesophagogastric junction. J Gastroenterol Hepatol 2000; 15 (07) 730-736
24 Dulak AM, Stojanov P, Peng S. , et al. Exome and whole-genome sequencing of esophageal adenocarcinoma identifies recurrent driver events and mutational complexity. Nat Genet 2013; 45 (05) 478-486
25 Sommerer F, Vieth M, Markwarth A. , et al. Mutations of BRAF and KRAS2 in the development of Barrett's adenocarcinoma. Oncogene 2004; 23 (02) 554-558
26 Trautmann B, Wittekind C, Strobel D. , et al. K-ras point mutations are rare events in premalignant forms of Barrett's oesophagus. Eur J Gastroenterol Hepatol 1996; 8 (08) 799-804
27 Janmaat ML, Gallegos-Ruiz MI, Rodriguez JA. , et al. Predictive factors for outcome in a phase II study of gefitinib in second-line treatment of advanced esophageal cancer patients. J Clin Oncol 2006; 24 (10) 1612-1619
28 Okines AF, Gonzalez de Castro D, Cunningham D. , et al. Biomarker analysis in oesophagogastric cancer: results from the REAL3 and TransMAGIC trials. Eur J Cancer 2013; 49 (09) 2116-2125
29 Chong IY, Cunningham D, Barber LJ. , et al. The genomic landscape of oesophagogastric junctional adenocarcinoma. J Pathol 2013; 231 (03) 301-310
30 Sekine S, Nakanishi Y, Ogawa R, Kouda S, Kanai Y. Esophageal melanomas harbor frequent NRAS mutations unlike melanomas of other mucosal sites. Virchows Arch 2009; 454 (05) 513-517
31 Preusser M, Berghoff AS, Capper D. , et al. No evidence for BRAF-V600E mutations in gastroesophageal tumors: results from a high-throughput analysis of 534 cases using a mutation-specific antibody. Appl Immunohistochem Mol Morphol 2013; 21 (05) 426-430
32 Schneider A, Michaud L, Gottrand F. Esophageal atresia: metaplasia, Barrett. Dis Esophagus 2013; 26 (04) 425-427
33 Ho TH, Dang KX, Lintula S. , et al. Extendable blocking probe in reverse transcription for analysis of RNA variants with superior selectivity. Nucleic Acids Res 2015; 43 (01) e4
34 Stenman J, Paju A, Rissanen O. , et al. Targeted gene-expression analysis by genome-controlled reverse transcription-PCR. Clin Chem 2006; 52 (11) 1988-1996
35 Gottrand F, Sfeir R, Coopman S, Deschildre A, Michaud L. [Outcome of children with repaired oesophageal atresia]. Arch Pediatr 2008; 15 (12) 1837-1842
36 Bos JL. Ras oncogenes in human cancer: a review. Cancer Res 1989; 49 (17) 4682-4689
37 Kressner U, Bjørheim J, Westring S. , et al. Ki-ras mutations and prognosis in colorectal cancer. Eur J Cancer 1998; 34 (04) 518-521
38 Fearon ER, Vogelstein B. A genetic model for colorectal tumorigenesis. Cell 1990; 61 (05) 759-767
39 Eser S, Schnieke A, Schneider G, Saur D. Oncogenic KRAS signalling in pancreatic cancer. Br J Cancer 2014; 111 (05) 817-822
40 Chen J, Guo F, Shi X. , et al. BRAF V600E mutation and KRAS codon 13 mutations predict poor survival in Chinese colorectal cancer patients. BMC Cancer 2014; 14: 802
41 Shigaki H, Baba Y, Watanabe M. , et al. KRAS and BRAF mutations in 203 esophageal squamous cell carcinomas: pyrosequencing technology and literature review. Ann Surg Oncol 2013; 20 (Suppl. 03) S485-S491
42 Arber N, Shapira I, Ratan J. , et al. Activation of c-K-ras mutations in human gastrointestinal tumors. Gastroenterology 2000; 118 (06) 1045-1050
43 Baba Y, Ishimoto T, Harada K. , et al. Molecular characteristics of basaloid squamous cell carcinoma of the esophagus: analysis of KRAS, BRAF, and PIK3CA mutations and LINE-1 methylation. Ann Surg Oncol 2015; 22 (11) 3659-3665
44 Maeng CH, Lee J, van Hummelen P. , et al. High-throughput genotyping in metastatic esophageal squamous cell carcinoma identifies phosphoinositide-3-kinase and BRAF mutations. PLoS One 2012; 7 (08) e41655
45 Andreyev HJ, Norman AR, Cunningham D, Oates JR, Clarke PA. Kirsten ras mutations in patients with colorectal cancer: the multicenter “RASCAL” study. J Natl Cancer Inst 1998; 90 (09) 675-684