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Status of the DPC4 tumor suppressor gene in sporadic colon adenocarcinoma of Croatian patients: identification of a novel somatic mutation.
Mutat Res 2004; 548(1-2):61-73MR

Abstract

Loss of heterozygosity (LOH) of loci on chromosome 18q occurs in a majority of colorectal cancers. The DPC4 (Smad4) tumor suppressor gene, located at 18q21.1, may be a predisposing gene for Juvenile Polyposis Syndrome. To investigate alterations of the DPC4 gene in sporadic colon adenocarcinoma, a panel of 60 tumor specimens from Croatian patients was surveyed for evidence of LOH and also for mutations within the entire DPC4 coding region (exons 1-11). Using three pairs of specific primers for the three DPC4 microsatellite repetitive sequences, we investigated the frequency of LOH. The presence of single nucleotide change at restriction sites of specific codons in exons 2, 8, 10, and 11 (which belong to the conserved region of the gene) was examined by RFLP analysis. The investigation was extended to search for any other mutation within the entire coding region of the DPC4 gene by single strand conformation polymorphism (SSCP) analysis. Our results show a high frequency of heterozygosity in 58 of 60 (97%) colon adenocarcinoma samples. LOH at any one of the three flanking markers was observed in 26 (45%) of the 58 informative cases. The loss of one allele of the DPC4 gene was negatively correlated with tumor size; more frequent in smaller tumors (<5 cm) than in larger ones. A mutation was found in exon 11 in only one tumor sample (T18), and the mutation was verified by sequencing. Sequencing demonstrated a novel mutation-a deletion in exon 11 (134-153 del TAGACGAAGTACTTCATACC) of the DPC4 gene in the MH2 domain. These data suggest that inactivation of the DPC4 gene contributes to the genesis of colorectal carcinoma through allelic loss whereas mutation in the coding region of the DPC4 gene is infrequently detected in Croatian patients with A, B or C stages of colorectal cancers.

Authors+Show Affiliations

Division of Molecular Medicine, Rudjer Bosković Institute, Bijenicka c.54, 10000 Zagreb, Croatia. mhadzija@rudjer,irb.hrNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15063137

Citation

Popović Hadzija, Marijana, et al. "Status of the DPC4 Tumor Suppressor Gene in Sporadic Colon Adenocarcinoma of Croatian Patients: Identification of a Novel Somatic Mutation." Mutation Research, vol. 548, no. 1-2, 2004, pp. 61-73.
Popović Hadzija M, Radosevic S, Kovacević D, et al. Status of the DPC4 tumor suppressor gene in sporadic colon adenocarcinoma of Croatian patients: identification of a novel somatic mutation. Mutat Res. 2004;548(1-2):61-73.
Popović Hadzija, M., Radosevic, S., Kovacević, D., Lukac, J., Hadzija, M., Spaventi, R., ... Kapitanović, S. (2004). Status of the DPC4 tumor suppressor gene in sporadic colon adenocarcinoma of Croatian patients: identification of a novel somatic mutation. Mutation Research, 548(1-2), pp. 61-73.
Popović Hadzija M, et al. Status of the DPC4 Tumor Suppressor Gene in Sporadic Colon Adenocarcinoma of Croatian Patients: Identification of a Novel Somatic Mutation. Mutat Res. 2004 Apr 14;548(1-2):61-73. PubMed PMID: 15063137.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Status of the DPC4 tumor suppressor gene in sporadic colon adenocarcinoma of Croatian patients: identification of a novel somatic mutation. AU - Popović Hadzija,Marijana, AU - Radosevic,Senka, AU - Kovacević,Duje, AU - Lukac,Josip, AU - Hadzija,Mirko, AU - Spaventi,Radan, AU - Pavelić,Kresimir, AU - Kapitanović,Sanja, PY - 2003/05/19/received PY - 2003/12/30/revised PY - 2003/12/31/accepted PY - 2004/4/6/pubmed PY - 2004/5/21/medline PY - 2004/4/6/entrez SP - 61 EP - 73 JF - Mutation research JO - Mutat. Res. VL - 548 IS - 1-2 N2 - Loss of heterozygosity (LOH) of loci on chromosome 18q occurs in a majority of colorectal cancers. The DPC4 (Smad4) tumor suppressor gene, located at 18q21.1, may be a predisposing gene for Juvenile Polyposis Syndrome. To investigate alterations of the DPC4 gene in sporadic colon adenocarcinoma, a panel of 60 tumor specimens from Croatian patients was surveyed for evidence of LOH and also for mutations within the entire DPC4 coding region (exons 1-11). Using three pairs of specific primers for the three DPC4 microsatellite repetitive sequences, we investigated the frequency of LOH. The presence of single nucleotide change at restriction sites of specific codons in exons 2, 8, 10, and 11 (which belong to the conserved region of the gene) was examined by RFLP analysis. The investigation was extended to search for any other mutation within the entire coding region of the DPC4 gene by single strand conformation polymorphism (SSCP) analysis. Our results show a high frequency of heterozygosity in 58 of 60 (97%) colon adenocarcinoma samples. LOH at any one of the three flanking markers was observed in 26 (45%) of the 58 informative cases. The loss of one allele of the DPC4 gene was negatively correlated with tumor size; more frequent in smaller tumors (<5 cm) than in larger ones. A mutation was found in exon 11 in only one tumor sample (T18), and the mutation was verified by sequencing. Sequencing demonstrated a novel mutation-a deletion in exon 11 (134-153 del TAGACGAAGTACTTCATACC) of the DPC4 gene in the MH2 domain. These data suggest that inactivation of the DPC4 gene contributes to the genesis of colorectal carcinoma through allelic loss whereas mutation in the coding region of the DPC4 gene is infrequently detected in Croatian patients with A, B or C stages of colorectal cancers. SN - 0027-5107 UR - https://www.unboundmedicine.com/medline/citation/15063137/Status_of_the_DPC4_tumor_suppressor_gene_in_sporadic_colon_adenocarcinoma_of_Croatian_patients:_identification_of_a_novel_somatic_mutation_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0027510704000259 DB - PRIME DP - Unbound Medicine ER -