GENESIS: Genetic Biopsy for Prediction of Surveillance Intervals After Endoscopic Resection of Colonic Polyps (GENESIS)

Colorectal cancer ist the 2nd most leading cancer among men and women in germany. Screening colonoscopy has the potential to detect premalignant lesions. By endoscopical resection of these lesions, colorectal cancers could be avoided. The decision for surveillance is made according to patients medical history, amount and histological characteristics of the resected polyps. Molecular guided decisions are still missing. Thus, further tools and mechanisms, beyond but in addition to endoscopy and histopathological, are strongly required to reduce such interval carcinomas and get a better and deeper inside into molecular alterations which occurs in premalignant lesions in the colon and describe risk populations which might benefit from shorter surveillance strategies by colonoscopy. Therefore GENESIS will enroll 100 patients, which underwent screening colonoscopy with polyp ectomy. All biopsies were stored and processed without formalin in special boxes (PaxGene by Qiagen®). After microdissection of polyp tissue and isolation of DNA targeted next generation sequencing of 38 cancer-related genes followed by bioinformatics and systems biology analyses. The sequencing results were correlated to the endoscopical and histopathological findings. In parallel we are collecting EDTA-blood samples for analysis of circulating cell-free DNA (cfDNA) to investigate the potential of liquid biopsies in premalignant colorectal lesions.

Study Overview

• Status: Completed
• Conditions: Colonic Polyps
• Intervention / Treatment: Genetic: Polypectomy and NGS

Detailed Description

Colorectal cancer ist the 2nd most leading cancer among men and women in germany. Screening colonoscopy is provided for all people over 55 years in germany to detect and remove precancerous lesions (polyps) and thereby prevent the occurence of colorectal cancers. According to the result of screening colonoscopy and histopathological examination of the removed polyps the next examination will be planned. But so called interval carcinomas were observed with increasing incidence. Thus, further tools and mechanisms, beyond but in addition to endoscopy and histopathology, are strongly required to reduce such interval carcinomas and get a better and deeper inside into molecular alterations which occurs in premalignant lesions in the colon and describe risk populations which might benefit from shorter surveillance strategies by colonoscopy. Therefore we will enroll 100 patients, which underwent screening colonoscopy with polyp ectomy. Each polyp, provided for endoscopical removal, well be biopsied and stored separately. In each case, diagnosis is ensured. Per patient a maximum of 6 biopsies (from 6 different polyps) is intended. All biopsies were stored and processed without formalin in special boxes (PaxGene by Qiagen®). After microdissection of polyp tissue and isolation of DNA targeted next generation sequencing of 38 genes (ACVR1B, DCC, MIER3, SLC9A9, AKT1, DMD, MLH1, SMAD2, APC, EP300, MSH2, SMAD4, ATM, ERBB2, MSH3, TCERG1, ATP6V0D2, FBXW7, MSH6, TCF7L2, BAX, FZD3, MYO1B, TGFBR2, BRAF, GPC6, NRAS, TP53, CASP8, KRAS, PIK3CA, WBSCR17, CDC27, MAP2K4, PIK3R1, CTNNB1, MAP7, PTPN12) followed by bioinformatics and systems biology analyses. The sequencing results were correlated to the endoscopical and histopathological findings. In parallel we are collecting EDTA-blood samples for analysis of circulating cell-free DNA (cfDNA). NGS targeted sequencing of these 38 genes should also be performed on cfDNA level to investigate the potential of liquid biopsies in premalignant colorectal lesions.

• Study Type: Interventional
• Enrollment (Actual): 101
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Austria
  • Steiermark
    • Graz, Steiermark, Austria, 8036
      • Medical University Graz
• Germany
  • Baden-Württemberg
    • Dornstadt, Baden-Württemberg, Germany, 89160
      • Specialized Medical Office for Gastroenterology
    • Ulm, Baden-Württemberg, Germany, 89081
      • University Ulm, Internal Medicine I, Interventional and Experimental Endoscopy (InExEn)
  • Bavaria
    • Munich, Bavaria, Germany, 81675
      • Technical University Munich

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• written informed consent
• indication of screening colonoscopy

Exclusion Criteria:

• chronic inflammatory bowl disease
• known colorectal cancer (except curative treated colorectal cancers more than 5 years ago)
• disagreement in participation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: SCREENING
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Polypectomy and NGS; All patients which underwent screening colonoscopy and fulfilling the inclusion criteria are eligible. Polyps were biopsied and underwent histopathological and genetic analyses	Genetic: Polypectomy and NGS; NGS of 38 cancer-related genes, systems biological analyses, correlation genetics to pathology and clinical data

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Genetic landscape of colonic polyps based on NGS-analysis	Are we able to describe risk populations based on clinical, histopathological and sequencing data which might bring a benefit for these cohort for shorter surveillance strategies by colonoscopy? What are the similarities in the altered genes, what are the differences? Are we able to define common signaling hubs?	1 year

Collaborators and Investigators

• Sponsor: University of Ulm
• Collaborators: Medical University of Graz; Technical University of Munich; QIAGEN Gaithersburg, Inc; Specialized Medical Office for Gastroenterology Dornstadt
• Investigators: Principal Investigator: Alexander G. Meining, Prof. Dr., University Ulm, Internal Medicine I, Interventional and Experimental Endoscopy (InExEn)

Study record dates

Study Major Dates

• Study Start: August 1, 2015
• Primary Completion (Actual): August 1, 2016
• Study Completion (Actual): October 1, 2016

Study Registration Dates

• First Submitted: October 29, 2015
• First Submitted That Met QC Criteria: November 2, 2015
• First Posted (Estimate): November 3, 2015

Study Record Updates

• Last Update Posted (Estimate): November 3, 2016
• Last Update Submitted That Met QC Criteria: November 2, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: colorectal cancer; liquid biopsy; next generation sequencing; screening colonoscopy; colorectal adenoma; surveillance strategies
• Additional Relevant MeSH Terms: Pathological Conditions, Anatomical; Intestinal Polyps; Polyps; Colonic Polyps
• Other Study ID Numbers: GENESIS