BRCA1/2 mutation screening in high-risk breast/ovarian cancer families and sporadic cancer patient surveilling for hidden high-risk families

Abstract

BackgroundThe estimated ratio of hereditary breast/ovarian cancer (HBOC) based on family history is 1.5% in Latvia. This is significantly lower than the European average of 5–10%. Molecular markers like mutations and SNPs can help distinguish HBOC patients in the sporadic breast and ovarian cancer group.Methods50 patients diagnosed with HBOC in the Latvian Cancer Registry from January 2005 to December 2008 were screened for BRCA1 founder mutation-negatives and subjected to targeted resequencing of BRCA1 and BRCA2 genes. The newly found mutations were screened for in the breast and ovarian cancer group of 1075 patients by Real Time-PCR/HRM analysis and RFLP.ResultsFour BRCA2 mutations including three novel BRCA2 frameshift mutations and one previously known BRCA2 frameshift mutation and one BRCA1 splicing mutation were identified. Two of the BRCA2 mutations were found in a group of consecutive breast cancer patients with a frequency of 0.51% and 0.38%.ConclusionsMolecular screening of sequential cancer patients is an important tool to identify HBOC families.

High expression of miR-214 is associated with a worse disease-specific survival of the triple-negative breast cancer patients

“…The BRCA1 gene mutations (5382insC, 4153delA, and C61G) were determined by multiplex polymerase chain reaction [ 31 ]. Breast cancer patients with the BRCA1 gene mutations were defined as hereditary [ 31 ].…”

High frequency of pathogenic non-founder germline mutations in BRCA1 and BRCA2 in families with breast and ovarian cancer in a founder population

“…In seven out of sixteen (44%) primary breast and ovarian cancer patients matching the criteria for BRCA1/2 testing pathogenic non-founder BRCA1/2 mutations were identified. All 7 pathogenic mutations, including 2 large deletions, are novel in populations of Latvia [ 5 , 8 ]. These results may suggest that the present practice of testing only the 3 most frequent BRCA1 pathogenic founder mutations is insufficient and fails to detect a considerable number of pathogenic mutations in BRCA1/2 .…”

“…There is little information about pathogenic BRCA1/2 non-founder mutations in Latvia. In a study published by Berzina et al, pathogenic non-founder mutations in BRCA1 and BRCA2 were identified in 4 out of 30 high-risk breast/ovarian cancer families from the Latvian population [ 8 ]. In another study published by Tihomirova et al, non-founder pathogenic mutations in BRCA1 and BRCA2 were detected in 9 out of 160 patients with breast and ovarian cancer [ 5 ].…”

Segmentation of Hematoxylin-Eosin stained breast cancer histopathological images based on pixel-wise SVM classifier

“…Breast cancer (BC) is the most commonly diagnosed malignant tumor among females in the world, and its morbidity is increasing in many countries [1]. When a patient is suspected of suffering from BC, clinicians can get diagnostic information from (i) diagnostic radiology, (ii) histopathology and cytopathology, and (iii) molecular and genetic techniques [2]. Among existing diagnostic technologies, histopathologic image of a biopsy or surgical specimen is the routine diagnostic method, and Hematoxylin-Eosin (HE) staining remains the gold criterion for BC diagnosis and grading [3].…”