title: Genomic instability and oncogene amplifications in colorectal adenomas predict recurrence and synchronous carcinoma.
abstract: Individual colorectal adenomas have different propensities to progress to invasive disease. In this study, we explored whether these differences could be explained by gene copy number alterations. We evaluated 18 adenomas of patients without synchronous or subsequent carcinoma (6.5 years follow-up), 23 adenomas of carcinoma patients, and 6 related carcinomas. All samples were measured for their DNA ploidy status. Centromere probes for chromosomes 17 and 18, as well as gene-specific probes for SMAD7, EGFR, NCOA3, TP53, MYC, and RAB20 were assessed by multicolor fluorescence in situ hybridization. An increased genomic instability index of CEP17, SMAD7, and EGFR, as well as TP53 deletions and MYC amplifications defined adenomas of patients with synchronous carcinoma (P<0.05). Diploid NCOA3 signal counts were associated with longer adenoma recurrence-free surveillance (P=0.042). In addition, NCOA3, MYC, EGFR, and RAB20 amplifications, as well as TP53 deletions correlated with increased DNA stem line values and/or aneuploidy in adenomas (P<0.05). Furthermore, aberrations of NCOA3, MYC, and RAB20 were associated with histopathologically defined high-risk adenomas (P<0.05). RAB20 amplifications were also correlated with high-grade dysplastic adenomas (P=0.002). We conclude that genomic instability in colorectal adenomas is reflected by EGFR, MYC, NCOA3, and RAB20 amplifications that do correlate with histomorphological features and are indicative for adenoma recurrence and the presence of synchronous carcinomas.
authors.affiliation: Department of Surgery, University Clinic Schleswig-Holstein, Campus Lübeck, Lübeck, Germany. Jens.Habermann@gmail.com
authors.forename: Jens K
authors.initials: JK
authors.lastname: Habermann
authors.forename: Constanze A
authors.initials: CA
authors.lastname: Brucker
authors.forename: Sandra
authors.initials: S
authors.lastname: Freitag-Wolf
authors.forename: Kerstin
authors.initials: K
authors.lastname: Heselmeyer-Haddad
authors.forename: Stefan
authors.initials: S
authors.lastname: Krüger
authors.forename: Linda
authors.initials: L
authors.lastname: Barenboim
authors.forename: Tricia
authors.initials: T
authors.lastname: Downing
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Bruch
authors.forename: Gert
authors.initials: G
authors.lastname: Auer
authors.forename: Uwe J
authors.initials: UJ
authors.lastname: Roblick
authors.forename: Thomas
authors.initials: T
authors.lastname: Ried
mesh_terms: D000236:Adenoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D016009:Chi-Square Distribution; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D018450:Disease Progression; D005260:Female; D005784:Gene Amplification; D042822:Genomic Instability; D005858:Germany; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D009378:Neoplasms, Multiple Primary; D009857:Oncogenes; D011003:Ploidies; D011379:Prognosis; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors