TY - JOUR
T1 - Allelotype analysis of oesophageal adenocarcinoma
T2 - Loss of heterozygosity occurs at multiple sites
AU - Dolan, K.
AU - Garde, J.
AU - Gosney, J.
AU - Sissons, M.
AU - Wright, T.
AU - Kingsnorth, A. N.
AU - Walker, S. J.
AU - Sutton, R.
AU - Meltzer, S. J.
AU - Field, J. K.
N1 - Funding Information:
KD is supported by Ursula Keyes Trust. UK. JG is supported by North West Health Authority. UK and NIH arants #CA67497. #DK47717 and #CA78843. SJM is supported by The Office of Medical Research. Department of Veterans Affairs. USA.
PY - 1998
Y1 - 1998
N2 - Deletions of tumour-suppressor genes can be detected by loss of heterozygosity (LOH) studies, which were performed on 23 cases of adenocarcinoma of the oesophagus, using 120 microsatellite primers covering all non-acrocentric autosomal chromosome arms. The chromosomal arms most frequently demonstrating LOH were 3p (64% of tumours), 5q (45%), 9p (52%), 11p (61%), 13q (50%), 17p (96%), 17q (55%) and 18q (70%). LOH on 3p, 9p, 13q, 17p and 18q occurred mainly within the loci of the VHL, CDKN2, Rb, TP53 and DCC tumour-suppressor genes respectively LOH on 5q occurred at the sites of the MSH3 mismatch repair gene and the APC tumour-suppressor gene. 11p15.5 and 17q25-qter represented areas of greatest LOH on chromosomes 11p and 17q, and are putative sites of novel tumour-suppressor genes. LOH on 9p was significantly associated with LOH on 5q, and tumours demonstrating LOH at both the CDKN2 (9p21) and MSH3 (5q11-q12) genes had a significantly higher fractional allele loss than those retaining heterozygosity at these sites. Six of nine carcinomas displaying microsatellite alterations also demonstrated LOH at CDKN2, which may be associated with widespread genomic instability. Overall, there are nine sites of LOH associated with oesophageal adenocarcinoma.
AB - Deletions of tumour-suppressor genes can be detected by loss of heterozygosity (LOH) studies, which were performed on 23 cases of adenocarcinoma of the oesophagus, using 120 microsatellite primers covering all non-acrocentric autosomal chromosome arms. The chromosomal arms most frequently demonstrating LOH were 3p (64% of tumours), 5q (45%), 9p (52%), 11p (61%), 13q (50%), 17p (96%), 17q (55%) and 18q (70%). LOH on 3p, 9p, 13q, 17p and 18q occurred mainly within the loci of the VHL, CDKN2, Rb, TP53 and DCC tumour-suppressor genes respectively LOH on 5q occurred at the sites of the MSH3 mismatch repair gene and the APC tumour-suppressor gene. 11p15.5 and 17q25-qter represented areas of greatest LOH on chromosomes 11p and 17q, and are putative sites of novel tumour-suppressor genes. LOH on 9p was significantly associated with LOH on 5q, and tumours demonstrating LOH at both the CDKN2 (9p21) and MSH3 (5q11-q12) genes had a significantly higher fractional allele loss than those retaining heterozygosity at these sites. Six of nine carcinomas displaying microsatellite alterations also demonstrated LOH at CDKN2, which may be associated with widespread genomic instability. Overall, there are nine sites of LOH associated with oesophageal adenocarcinoma.
KW - Fractional allele loss
KW - Loss of heterozygosity
KW - Oesophageal adenocarcinoma
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U2 - 10.1038/bjc.1998.607
DO - 10.1038/bjc.1998.607
M3 - Article
C2 - 9764589
AN - SCOPUS:0031659929
SN - 0007-0920
VL - 78
SP - 950
EP - 957
JO - British journal of cancer
JF - British journal of cancer
IS - 7
ER -