Genetic changes in breast carcinomas in an Icelandic population

Area of Science:

• Oncology
• Cancer Genetics
• Molecular Biology

Background:

• Genetic alterations in chromosomes 13 and 17 are implicated in breast cancer development.
• Specific genes like retinoblastoma (RB1) and p53, and the erbB2 oncogene, are frequently affected in various cancers.

Purpose of the Study:

• To investigate genetic changes, including allelic losses and mutations, in chromosomes 13 and 17 in breast tumor samples.
• To correlate these genetic alterations with family history, clinical factors, and prognosis in breast cancer patients.

Main Methods:

• Analysis of allelic losses at the RB1 locus (chromosome 13q) and on chromosome 17.
• Detection of erbB2 oncogene amplification.
• Identification of p53 gene mutations using constant denaturant gradient electrophoresis (CDGE).

Main Results:

• Allelic loss or rearrangement was detected in 37-51% of tumors, predominantly at 17p13.1 and 17p13.3.
• p53 gene mutations were found in 16% of tumors.
• Losses at the RB1 locus correlated with losses on chromosome 17; p53 mutations associated with erbB2 amplification.
• Tumor genetic alterations, specifically RB1 locus and chromosome 17 deletions, were linked to an increased breast cancer risk in relatives.

Conclusions:

• Losses at the RB1 locus and on chromosome 17 are associated with familial breast cancer risk.
• p53 mutations indicate a poor prognosis in this breast cancer patient cohort.
• No association was found between p53 mutations or erbB2 amplification and family history or prognosis.