title: A protocol for genetic evaluation of patients with multiple colorectal adenomas and without evidence of APC gene mutation.
abstract: BACKGROUND
  Patients with multiple (< 100) colorectal adenomatous polyps are at increased risk for colorectal cancer. Genetic evaluation of those patients who test negative forAPCgene mutation is both a clinical and economic burden but is critical for counseling and surveillance. In Israel, this is confounded by the fact that national health insurance does not fully cover genetic evaluation of APC gene exon 16.
  
  
  OBJECTIVE
  To perform a comprehensive genetic evaluation of APC gene mutation-negative polyposis patients with the aim of developing a future evaluation protocol.
  
  
  METHODS
  Genetic analyses were performed in 29 APC gene mutation-negative Jewish individuals with 5 to > or = 40 colonic adenomas who did not fulfill Amsterdam (clinical) criteria for Lynch syndrome. Analyses included completion of APC gene exon 16 sequencing, analysis for APC gene copy number variations (deletions or duplications), MUTYH gene sequencing, and microsatellite instability in CRC patients fulfilling "Bethesda" (laboratory investigation) criteria for Lynch syndrome.
  
  
  RESULTS
  Completion of APC gene exon 16 sequencing revealed one patient with the E1317Q polymorphism. All were normal by APC multiplex ligation-dependent probe amplification analysis. Pathogenic MUTYH mutations were found in three patients, all of North African origin; two additional patients had variants of unknown significance. One of six patients with Bethesda-positive criteria was MSI-High with immunohistology consistent with MLH1 mutation.
  
  
  CONCLUSIONS
  Based on this small but well-characterized cohort with multiple colorectal adenomas, Lynch syndrome needs to be excluded if there are compatible criteria; otherwise MUTYH sequencing is probably the first step in evaluating APC-negative patients, especially for Jews of North African descent. Completing APC exon 16 sequencing and copy number variations analysis should probably be the last evaluations.
authors.affiliation: Department of Gastroenterology, Sourasky Tel Aviv Medical Center, Tel Aviv University, Ramat Aviv, Israel.
authors.forename: Guy
authors.initials: G
authors.lastname: Rosner
authors.forename: Paul
authors.initials: P
authors.lastname: Rozen
authors.forename: Dani
authors.initials: D
authors.lastname: Bercovich
authors.forename: Chen
authors.initials: C
authors.lastname: Shochat
authors.forename: Irit
authors.initials: I
authors.lastname: Solar
authors.forename: Hana
authors.initials: H
authors.lastname: Strul
authors.forename: Revital
authors.initials: R
authors.lastname: Kariv
authors.forename: Zamir
authors.initials: Z
authors.lastname: Halpern
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D045647:DNA Glycosylases / Q000235:genetics*; D005260:Female; D017491:Genes, APC; D005820:Genetic Testing; D006801:Humans; D007557:Israel; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D011237:Predictive Value of Tests; D055815:Young Adult
chemical_list: D045647:DNA Glycosylases; C061738:mutY adenine glycosylase