title: Copy number of the Adenomatous Polyposis Coli gene is not always neutral in sporadic colorectal cancers with loss of heterozygosity for the gene.
abstract: BACKGROUND
  Changes in the number of alleles of a chromosome may have an impact upon gene expression. Loss of heterozygosity (LOH) indicates that one allele of a gene has been lost, and knowing the exact copy number of the gene would indicate whether duplication of the remaining allele has occurred. We were interested to determine the copy number of the Adenomatous Polyposis Coli (APC) gene in sporadic colorectal cancers with LOH.
  
  
  METHODS
  We selected 38 carcinomas with LOH for the APC gene region of chromosome 5, as determined by amplification of the CA repeat region within the D5S346 loci. The copy number status of APC was ascertained using the SALSA® MLPA® P043-B1 APC Kit. LOH for the DCC gene, KRAS gene mutation, and microsatellite instability were also evaluated for each tumor, utilizing standard polymerase chain reaction methods.
  
  
  RESULTS
  No tumor demonstrated microsatellite instability. LOH of the DCC gene was also present in 33 of 36 (91.7%) informative tumors. A KRAS gene mutation was present in 16 of the 38 (42.1%) tumors. Twenty-four (63.2%) of the tumors were copy number neutral, 10 (26.3%) tumors demonstrated major loss, while two (5.3%) showed partial loss. Two tumors (5.3%) had copy number gain.
  
  
  CONCLUSIONS
  Results of APC and DCC LOH, KRAS and microsatellite instability indicate our colorectal cancer cases were typical of sporadic cancers following the 'chromosomal instability' pathway. The majority of our colorectal carcinomas with LOH for APC gene are copy number neutral. However, one-third of our cases showed copy number loss, suggesting that duplication of the remaining allele is not required for the development of a colorectal carcinoma.
authors.affiliation: Department of Medicine, Saint Barnabas Medical Center, 22 Old Short Hills Road, Livingston, NJ, 07039, USA. pzauber@barnabashealth.org.
authors.forename: Peter
authors.initials: P
authors.lastname: Zauber
authors.affiliation: Department of Pathology, Saint Barnabas Medical Center, 100 Old Short Hills Road, Livingston, NJ, 07039, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Marotta
authors.affiliation: Department of Pathology, Saint Barnabas Medical Center, 100 Old Short Hills Road, Livingston, NJ, 07039, USA.
authors.forename: Marlene
authors.initials: M
authors.lastname: Sabbath-Solitare
mesh_terms: D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D043171:Chromosomal Instability / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D000075389:DCC Receptor; D056915:DNA Copy Number Variations / Q000235:genetics; D005260:Female; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D009154:Mutation; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D011956:Receptors, Cell Surface / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D025601:Adenomatous Polyposis Coli Protein; D000075389:DCC Receptor; C501909:DCC protein, human; C117307:KRAS protein, human; D011956:Receptors, Cell Surface; D025521:Tumor Suppressor Proteins; D016283:Proto-Oncogene Proteins p21(ras)
keywords: APC gene; Chromosomal number; Colon tumors; Genetic mutations; KRAS gene; Loss of genetic material