Aberrations in the mismatch repair genes and the clinical impact on oesophageal squamous carcinomas from a high incidence area in South Africa.
OBJECTIVE
To investigate the incidence of genetic aberrations in the DNA repair genes in a cohort of oesophageal cancers.


METHODS
One hundred oesophagectomy samples of squamous cell carcinoma were studied. Normal and tumour DNA were isolated using a standard phenol/chloroform extraction procedure. Six recommended microsatellite loci with high informativity were analysed. The following markers were used: D2S123 (2p), D3S659 (3p), D3S1255 (3p), Bat 25 (4q), Bat 26 (2p), and Bat 40 (1p). The results were analysed using software attached to an automated DNA sequencer. The molecular data were then correlated with clinicopathological parameters.


RESULTS
The incidence of microsatellite instability and loss of heterozygosity was very low. There was no significant correlation between the clinicopathological and molecular data. However, D2S123 genetic abnormalities were seen more frequently in both moderately and well differentiated tumours than in poorly differentiated tumours (p = 0.033). Follow up data were available for only 67 of the 100 patients. Fifty patients were alive and 17 patients had died.


CONCLUSIONS
Low frequencies of genetic aberrations in these mismatch repair loci are found in squamous carcinomas of the oesophagus from a high incidence area in South Africa.
Naidoo
R
R
Pfizer Molecular Biology Research Facility, Doris Duke Medical Research Institute, Nelson R Mandela School of Medicine, Faculty of Health Science, University of KwaZulu Natal, Private Bag 7, Congella 4013, Durban, South Africa. Naidoor@ukzn.ac.za
Ramburan
A
A
Reddi
A
A
Chetty
R
R
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020137:Base Pair Mismatch / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D002869:Chromosome Aberrations; D004260:DNA Repair / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics*; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D016629:Esophagectomy; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D016133:Polymerase Chain Reaction / Q000379:methods
D004273:DNA, Neoplasm
Cancer Res. 1998 Nov 15;58(22):5248-57
9823339
Anticancer Res. 2000 Jan-Feb;20(1A):213-7
10769657
Cancer Invest. 2002;20(1):102-9
11852992
Int J Cancer. 1995 Aug 22;64(4):286-9
7657394
J Cancer Res Clin Oncol. 2001 Oct;127(10):603-12
11599796
Clin Cancer Res. 2001 Apr;7(4):883-91
11309337
Genes Chromosomes Cancer. 1994 Jul;10(3):177-82
7522040
Cancer Res. 1999 Apr 15;59(8):1877-83
10213495
Cancer Res. 1992 Dec 1;52(23):6525-30
1423299
Oncogene. 1996 Feb 1;12(3):699-703
8637728
Oncology. 2003;64(3):275-9
12697969
Diagn Mol Pathol. 1999 Sep;8(3):131-7
10565684
J Clin Oncol. 2003 Mar 15;21(6):1174-9
12637487
Br J Cancer. 1997;75(9):1336-9
9155055
Pathol Oncol Res. 1999;5(3):193-6
10491016
Ann N Y Acad Sci. 2003 Mar;983:213-9
12724226
Cell Cycle. 2003 May-Jun;2(3):202-10
12734426
Diabetes. 1992 Jun;41(6):742-9
1350258
Oncology. 1999;56(2):164-8
9949304
Mutat Res. 2001 Mar;488(1):77-85
11223406
Cell. 1990 Jun 1;61(5):759-67
2188735
Int J Cancer. 1998 Nov 23;78(5):544-9
9808520
Cancer Genet Cytogenet. 2003 Jan 1;140(1):23-30
12550754
Cancer Res. 1994 Jun 1;54(11):2996-3000
8187088
Cancer Res. 1995 Feb 15;55(4):891-4
7850805
Cancer Res. 1991 Apr 15;51(8):2113-7
1826231
Am J Gastroenterol. 2000 Nov;95(11):3266-75
11095352