High frequency allelic loss on chromosome 17p13.3-p11.1 in esophageal squamous cell carcinomas from a high incidence area in northern China

Huang, Jing; Hu, Nan; Goldstein, Alisa M.; Emmert‐Buck, Michael R.; Tang, Ze-Zhong; Roth, Mark J.; Wang, Quanhong; Dawsey, Sanford M.; Han, Xiao-You; Ding, Ti; Li, Guang; Giffen, Carol; Taylor, Philip R.

doi:10.1093/carcin/21.11.2019

Cited by 35 publications

(37 citation statements)

References 19 publications

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“…In addition, single-strand conformation polymorphism (SSCP) plus DNA sequencing were performed to identify variants along the entire coding sequence. The demographic characteristics of these original 56 esophageal squamous cell carcinoma patients were previously described (15) along with TP53, BRCA2, and DICE1 gene mutation results (16 -18). Eighty additional esophageal squamous cell carcinoma patients and 232 healthy individuals (101 from Beijing and 131 from Yangcheng in Shanxi Province) were specifically analyzed for germ-line variants identified in the initial 56 esophageal squamous cell carcinomas.…”

Section: Methodsmentioning

confidence: 99%

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Comprehensive Characterization of Annexin I Alterations in Esophageal Squamous Cell Carcinoma

Flaig

et al. 2004

Clinical Cancer Research

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Purpose:The purpose is to characterize alterations of the annexin I gene, its mRNA, and protein expression in esophageal squamous cell carcinoma.Experimental Design: Fifty-six cases of esophageal squamous cell carcinoma were analyzed using four microsatellite markers flanking the annexin I gene (9q11-q21) to identify loss of heterozygosity. In addition, we performed (a) single-strand conformation polymorphism and DNA sequencing along the entire promoter sequence and coding region to identify mutations, (b) real-time quantitative reverse transcription-PCR of RNA from frozen esophageal squamous cell carcinoma tissue (n ‫؍‬ 37) and in situ hybridization (n ‫؍‬ 5) on selected cases to assess mRNA expression, and (c) immunohistochemistry (n ‫؍‬ 44) to evaluate protein expression. The prevalence of the allelic variants identified in the first 56 patients was refined in 80 additional esophageal squamous cell carcinoma patients and 232 healthy individuals.Results: Forty-six of 56 (82%) esophageal squamous cell carcinoma patients showed loss of an allele at one or more of the four microsatellite markers; however, only one (silent) mutation was seen. Two intragenic variants were identified with high frequency of allelic loss (A58G, 64%; L109L, 69%). Thirty of 37 (81%) esophageal squamous cell carcinoma patients showed reduced annexin I mRNA expression, which was confirmed by in situ hybridization, whereas annexin I protein expression was reduced in 79% of poorly differentiated tumor cell foci but in only 5% of well-differentiated tumor foci, although allelic loss on chromosome 9 was found in both tumor grades.Conclusions: Allelic loss of annexin I occurs frequently, whereas somatic mutations are rare, suggesting that annexin I is not inactivated in esophageal squamous cell carcinoma via a two-hit mechanism. A decrease in annexin I protein expression was confirmed, consistent with a quantitative decrease in mRNA expression, and appeared to be related to tumor cell differentiation. We conclude that annexin I is not the tumor suppressor gene corresponding to the high levels of loss of heterozygosity observed on chromosome 9 in esophageal squamous cell carcinoma; however, dysregulation of mRNA and protein levels is associated with this tumor type.

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Section: Methodsmentioning

confidence: 99%

“…Tumor cells were harvested using LCM and DNA was extracted using methods described previously (15,19).…”

Section: Methodsmentioning

confidence: 99%

Comprehensive Characterization of Annexin I Alterations in Esophageal Squamous Cell Carcinoma

Flaig

et al. 2004

Clinical Cancer Research

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“…A total of 56 ESCC patients, including 34 males and 22 females, were evaluated. Details on these patients have been previously reported (Huang et al, 2000).…”

Section: Patient Selectionmentioning

confidence: 99%

“…Laser microdissection and extraction of DNA Tumor cells were microdissected under light microscopic visualization using methods previously described (EmmertBuck et al 1996;Huang et al, 2000).…”

Section: Biologic Specimen Collection and Processingmentioning

confidence: 99%

“…DNA extracted from tumor cells was microdissected from resection specimens, and genomic DNA extracted from venous blood was used for each patient. PCR reactions were carried out as previously reported (Huang et al, 2000). LOH was defined as either complete or nearly complete loss of a band in the tumor sample relative to the corresponding normal DNA.…”

Section: Markers Polymerase Chain Reaction (Pcr) and Loh Reading Anmentioning

confidence: 99%

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Allelic loss on chromosome 13q14 and mutation in deleted in cancer 1 gene in esophageal squamous cell carcinoma

et al. 2003

Oncogene

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Previous studies have shown frequent allelic loss on chromosome 13 in esophageal squamous cell carcinoma (ESCC). We assessed the frequency of allelic loss on chromosome 13q14 and mutations of deleted in cancer 1 (DICE1) (also found on 13q14) in ESCC patients to determine if this candidate tumor suppressor gene has a role in the development of ESCC, and whether this gene was an inactivation target for allelic loss on chromosome 13q14. Initially, we examined allelic loss at five markers flanking DICE1 in 56 ESCC patients from Shanxi Province, China, and then examined the entire coding sequence of this gene for mutations using polymerase chain reaction-single-strand confirmation polymorphism (PCR-SSCP) analysis and DNA sequencing. Subsequently, we extended our evaluation to an additional 80 ESCC patients and 232 healthy individuals to confirm the germline variant found in the initial 56 ESCC patients. The frequencies of allelic loss were 71, 58, and 75% for D13S325, D13S757, and D13S887, respectively, in the initial 56 ESCC patients studied. Overall, 73% of informative patients had loss of heterozygosity (LOH) for at least one of these three markers. Somatic mutations were identified in three patients (3/56, 5%), and one novel polymorphism was identified in 3% of ESCC patients (4/ 136) and 3% of healthy individuals (6/232). We conclude that DICE1 mutations occur in ESCC but are infrequent. The candidate tumor suppressor gene corresponding to the frequent allelic loss on chromosome 13q14 in ESCC remains unknown.

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High frequency of CDKN2A alterations in esophageal squamous cell carcinoma from a high‐risk Chinese population

Wang

et al. 2003

Genes Chromosomes & Cancer

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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.

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High frequency allelic loss on chromosome 17p13.3-p11.1 in esophageal squamous cell carcinomas from a high incidence area in northern China

Cited by 35 publications

References 19 publications

Comprehensive Characterization of Annexin I Alterations in Esophageal Squamous Cell Carcinoma

Comprehensive Characterization of Annexin I Alterations in Esophageal Squamous Cell Carcinoma

Allelic loss on chromosome 13q14 and mutation in deleted in cancer 1 gene in esophageal squamous cell carcinoma

High frequency of CDKN2A alterations in esophageal squamous cell carcinoma from a high‐risk Chinese population

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