Positive correlation between allelic loss at chromosome 14q24-31 and poor prognosis of patients with renal cell carcinoma.
OBJECTIVE
To report our development of a new application of the inter-Alu long polymerase chain reaction (PCR) for genomic scanning to screen for tumor-specific alterations in tumor DNA. Using this method, we detected a rearranged chromosomal region in renal cell carcinomas (RCCs). We then examined tumor-specific allelic loss in this region using microsatellite markers and determined whether a relationship was present between this allelic loss and the clinicopathologic features of the patients.


METHODS
The inter-Alu long PCR genomic scan method was performed using RCC DNA samples and primers specific for a minor subset of the human repeat sequence Alu. We analyzed DNA samples from 42 pairs of matched normal and nonpapillary RCC tissues with seven microsatellite markers.


RESULTS
The inter-Alu long PCR genomic scan method revealed an altered DNA region on chromosome 14q24-31, which is the location of several putative tumor suppressor genes. At least one of seven microsatellite markers on chromosome 14q24-31 showed loss of heterozygosity in 23 (54.8%) of 42 informative cases of RCC. The prevalent loss region was confined to a 2-Mb region around D14S67. We found a positive correlation between the presence of the loss of heterozygosity on 14q24-31 and tumor stage (P <0.05). We also found that cases with allelic loss at 14q24-31 had a poor prognosis (P = 0.045).


CONCLUSIONS
Our inter-Alu long PCR genomic scan method is a powerful method for the screening of DNA alterations, and our data suggest that the chromosome 14q24-31 region contains likely tumor suppressor genes associated with the progression of RCC.
Kaku
Haruki
H
Department of Molecular Genetics, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan.
Ito
Sachio
S
Ebara
Shin
S
Ouchida
Mamoru
M
Nasu
Yasutomo
Y
Tsushima
Tomoyasu
T
Kumon
Hiromi
H
Shimizu
Kenji
K
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020087:Alu Elements; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000401:mortality; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics* / Q000648:ultrastructure; D018450:Disease Progression; D020224:Expressed Sequence Tags; D005260:Female; D005500:Follow-Up Studies; D016147:Genes, Tumor Suppressor; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000401:mortality; D015993:Life Tables; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D016133:Polymerase Chain Reaction / Q000379:methods; D018807:Polymorphism, Single-Stranded Conformational; D011379:Prognosis; D021101:Radiation Hybrid Mapping; D016019:Survival Analysis