title: High frequency of CDKN2A alterations in esophageal squamous cell carcinoma from a high-risk Chinese population.
abstract: Because previous studies have shown that loss of heterozygosity (LOH) is common on chromosome arm 9p in esophageal squamous cell carcinoma (ESCC) and that genetic alterations in CDKN2A and CDKN2B on 9p are also common, we sought to determine whether LOH and these genetic alterations are related. We performed LOH studies on chromosome bands 9p21-p22 and searched for genetic alterations of CDKN2A and CDKN2B in 56 ESCCs from a high-risk Chinese population. Seventy-three percent of patients were found to have LOH at one or more loci on chromosome bands 9p21-p22, and LOH occurred more frequently in patients with a family history of upper gastrointestinal cancer than in those with a negative family history (P = 0.01, global permutation test). CDKN2A mutations (point mutations, deletions, insertions) were observed in 25% (14 of 56) of cases, and the LOH pattern was significantly different for individuals with and without a CDKN2A mutation (P = 0.01, global test). Three new single nucleotide polymorphisms (SNPs) and 2 previously reported SNPs were identified in this group of patients. Intragenic allelic loss at polymorphic sites in CDKN2A was detected in 32% (18 of 56) of patients. Seven of the 56 (13%) cases exhibited what is considered classic evidence (n = 4) or showed potential evidence (n = 3) of biallelic inactivation. Only one alteration was observed in CDKN2B, G171A in the 5' untranslated region. Both mutation and intragenic allelic loss in CDKN2A appear to play a role in the development of ESCC.
authors.affiliation: Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892-7236, USA.
authors.forename: Nan
authors.initials: N
authors.lastname: Hu
authors.forename: Chaoyu
authors.initials: C
authors.lastname: Wang
authors.forename: Hua
authors.initials: H
authors.lastname: Su
authors.forename: Wen-Jun
authors.initials: WJ
authors.lastname: Li
authors.forename: Michael R
authors.initials: MR
authors.lastname: Emmert-Buck
authors.forename: Guang
authors.initials: G
authors.lastname: Li
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Roth
authors.forename: Ze-Zhong
authors.initials: ZZ
authors.lastname: Tang
authors.forename: Ning
authors.initials: N
authors.lastname: Lu
authors.forename: Carol
authors.initials: C
authors.lastname: Giffen
authors.forename: Paul S
authors.initials: PS
authors.lastname: Albert
authors.forename: Philip R
authors.initials: PR
authors.lastname: Taylor
authors.forename: Alisa M
authors.initials: AM
authors.lastname: Goldstein
mesh_terms: D000483:Alleles; D044466:Asian People / Q000235:genetics; D024682:BRCA2 Protein / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics; D002681:China; D002871:Chromosome Banding / Q000379:methods; D002872:Chromosome Deletion; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D004938:Esophageal Neoplasms / Q000235:genetics*; D005260:Female; D005787:Gene Frequency / Q000235:genetics*; D019942:Genes, p16; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D018807:Polymorphism, Single-Stranded Conformational; D011159:Population Surveillance; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D025521:Tumor Suppressor Proteins
chemical_list: D024682:BRCA2 Protein; C493966:CDKN2B protein, human; D018797:Cell Cycle Proteins; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins