Mutations of the BRCA1 and BRCA2 genes in patients with bilateral breast cancer

Mutations of the BRCA1 or BRCA2 genes have been shown to strongly predispose towards the development of contralateral breast cancer in patients from large multi-case families. In order to test the hypothesis that BRCA1 and BRCA2 mutations are more frequent in patients with bilateral breast cancer, we have investigated a hospital-based series of 75 consecutive patients with bilateral breast cancer and a comparison group of 75 patients with unilateral breast cancer, pairwise matched by age and family history, for mutations in the BRCA1 and BRCA2 genes. Five frameshift deletions (517delGT in BRCA1; 4772delA, 5946delCT, 6174delT and 8138del5 in BRCA2) were identified in patients with bilateral disease. No further mutations, apart from polymorphisms and 3 rare unclassified variants, were found after scanning the whole BRCA1 and BRCA2 coding sequence. Three pathogenic BRCA1 mutations (Cys61Gly, 3814del5, 5382insC) were identified in the group of patients with unilateral breast cancer. The frequencies of common BRCA1 and BRCA2 missense variants were not different between the 2 groups. In summary, we did not find a significantly increased prevalence of BRCA1 and BRCA2 mutations in a hospital-based cohort of German patients with bilateral breast cancer. We conclude that bilaterality of breast cancer on its own is not strongly associated with BRCA1 and BRCA2 mutations when adjusted for age and family history. The high frequency of bilateral disease in multi-case breast cancer families may be due to a familial aggregation of additional susceptibility factors modifying the penetrance of BRCA1 and BRCA2 mutations. © 2001 Cancer Research Campaignhttp://www.bjcancer.co

Human BRCA1-associated breast cancer: No increase in numerical chromosomal instability compared to sporadic tumors

BRCA1 is a major gatekeeper of genomic stability. Acting in multiple central processes like double-strand break repair, centrosome replication, and checkpoint control, BRCA1 participates in maintaining genomic integrity and protects the cell against genomic instability. Chromosomal instability (CIN) as part of genomic instability is an inherent characteristic of most solid tumors and is also involved in breast cancer development. In this study, we determined the extent of CIN in 32 breast cancer tumors of women with a BRCA1 germline mutation compared to 62 unselected breast cancers. We applied fluorescence in situ hybridization (FISH) with centromere-specific probes for the chromosomes 1, 7, 8, 10, 17, and X and locus-specific probes for 3q27 (BCL6), 5p15.2 (D5S23), 5q31 (EGR1), 10q23.3 (PTEN), and 14q32 (IGH@) on formalin-fixed paraffin-embedded tissue microarray sections. Our hypothesis of an increased level of CIN in BRCA1-associated breast cancer could not be confirmed by this approach. Surprisingly, we detected no significant difference in the extent of CIN in BRCA1-mutated versus sporadic tumors. The only exception was the CIN value for chromosome 1. Here, the extent of CIN was slightly higher in the group of sporadic tumors

Whole-body hybrid positron emission tomography imaging yields clinically relevant information in the staging and restaging of sinonasal tumors

BACKGROUND Whole-body hybrid positron emission tomography (PET) imaging is increasingly used for sinonasal tumors. However, only empirical data exist on the additional, clinically relevant information derived from these techniques. METHODS This study included 96 regionalized magnetic resonance imaging (MRI) of the sinonasal tract/neck and separate hybrid FDG-PET/CT or FDG-PET/MRI in 74 patients. Additional radiological information (ARI) obtained from each hybrid examination was analyzed and its clinically relevance was determined. Clinically relevant information (CRI) was categorized with regard to primary tumor site, regional lymph node metastases, distant metastases, second primary tumors, and non-neoplastic findings. RESULTS A total of 45/96 (46.9%) hybrid PET examinations revealed ARI. CRI was found in 32/96 (33.3%) examinations and concerned the primary tumor site (6.1%), regional lymph node metastases (4.1%), distant metastases (14.3%), second primary tumors (7.3%), and non-neoplastic findings (5.1%). CONCLUSIONS Hybrid PET imaging yields additional radiological information translating into clinically relevant information in a substantial proportion of patients with sinonasal tumors