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

Abstract

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.

Monochromosome Transfer and Microarray Analysis Identify a Critical Tumor-Suppressive Region Mapping to Chromosome 13q14 and THSD1 in Esophageal Carcinoma

“…In contrast to the high LOH reported at the RB1 locus (16), RB1 protein expression was absent in only a small subset (6.4%, 11 of 172) of ESCC patients by immunohistochemical staining (17). RB1 is outside the 13q14 LOH region mapped by Li et al (9). Thus, these studies suggest that unknown novel TSG(s), other than RB1, are responsible for the high allelic loss at 13q14 and remain to be identified for ESCC tumorigenesis.…”

“…This current study is the first functional study of the tumor-suppressive role of chromosome 13 in ESCC and is initiated by the high-frequency ESCC chromosome 13q losses detected by comparative genomic hybridization (3) and loss of heterozygosity (LOH) studies (2,(6)(7)(8)(9). Comparative genomic hybridization analysis showed 100% losses on chromosome 13q in 17 ESCC cases (3).…”

Comprehensive Characterization of Annexin I Alterations in Esophageal Squamous Cell Carcinoma

“…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. Details of this set of patients and healthy individuals were also reported previously (18).…”

“…Extracted RNA was purified using RNeasy Mini kit (Qiagen, Inc., Valencia, CA) and Rnase-Free Dnase Set digestion (Qiagen, Inc.). Reverse transcription of RNA was performed by adding 5 g of total RNA, 1 L of oligo(dT) [12][13][14][15][16][17][18] (500 g/mL), 1 L (200 units) of the Superscript II reverse transcriptase,1 L (2 units) of Escherichia coli Rnase, and 1 L 10 mmol/L deoxynucleoside triphosphate (Invitrogen, Carlsbad, CA). All real-time PCR reactions were performed using an ABI Prism 7000 Sequence Detection System (PerkinElmer Applied Biosystems).…”

Promoter CpG hypermethylation and downregulation of DICE1 expression in prostate cancer

“…Recently, the tumor suppressor gene DICE1 (DDX26; OMIM *604331) was identified to colocalize with the microsatellite marker D13S284 in 13q14.3. This chromosomal region is frequently affected by allelic deletions in prostate cancer and other solid tumors (Ueda et al, 1999;Yin et al, 1999;Wieland et al, 2001;Li et al, 2003).…”