Deletion mapping in human renal cell carcinoma.

Area of Science:

• Oncology
• Human Genetics
• Molecular Biology

Background:

• Renal cell carcinoma (RCC) exhibits the highest incidence in Scandinavian populations.
• Cytogenetic studies consistently link RCC to abnormalities on chromosome 3p, particularly in hereditary and sporadic forms.
• Previous research indicated chromosome 3p alterations in RCC tumor tissues.

Purpose of the Study:

• To investigate chromosomal abnormalities in sporadic renal cell carcinoma (RCC) cases from Scandinavia.
• To confirm and extend previous findings regarding chromosome 3p deletions in RCC.
• To identify potential tumor suppressor gene locations involved in RCC oncogenesis.

Main Methods:

• Restriction fragment length polymorphism (RFLP) analysis was performed on tumor tissue from 23 sporadic Scandinavian RCC cases.
• Analysis included constitutional tissue from familial cases and tumor tissue from sporadic cases.
• All chromosomes were analyzed for losses of heterozygosity (LOH).

Main Results:

• Terminal deletions of chromosome 3p were observed in 68% of informative sporadic RCC cases.
• Loss of a Y chromosome locus was noted in 4 out of 14 male patients.
• Significant losses of heterozygosity were also detected on chromosomes 18 (5/15) and 17 (3/11), with lower frequencies on chromosomes 13, 10, and 11.
• A single familial case displayed reduplication of parts of chromosome 3p and chromosome 17.

Conclusions:

• The study confirms the high frequency of chromosome 3p deletions in sporadic RCC, reinforcing its role in oncogenesis.
• The data suggest that a tumor suppressor gene critical for RCC development is located distal to the DNF15S2 locus on chromosome 3p.
• No unique chromosomal findings specific to Scandinavian sporadic RCC cases were identified.