Genome-wide copy number aberrations and HER2 and FGFR1 alterations in primary breast cancer by molecular inversion probe microarray

Abstract

Breast cancer remains the second leading cause of cancer-related death in women despite stratification based on standard hormonal receptor (HR) and HER2 testing. Additional prognostic markers are needed to improve breast cancer treatment. Chromothripsis, a catastrophic genome rearrangement, has been described recently in various cancer genomes and affects cancer progression and prognosis. However, little is known about chromothripsis in breast cancer. To identify novel prognostic biomarkers in breast cancer, we used molecular inversion probe (MIP) microarray to explore genome-wide copy number aberrations (CNA) and breast cancer-related gene alterations in DNA extracted from formalin-fixed paraffin-embedded tissue. We examined 42 primary breast cancers with known HR and HER2 status assessed via immunohistochemistry and FISH and analyzed MIP microarray results for correlation with standard tests and survival outcomes. Global genome-wide CNA ranged from 0.2% to 65.7%. Chromothripsis-like patterns were observed in 23/38 (61%) cases and were more prevalent in cases with =10% CNA (20/26, 77%) than in cases with <10% CNA (3/12, 25%; p<0.01). Most frequently involved chromosomal segment was 17q12-q21, the HER2 locus. Chromothripsis-like patterns involving 17q12 were observed in 8/19 (42%) of HER2-amplified tumors but not in any of the tumors without HER2 amplification (0/19; p<0.01). HER2 amplification detected by MIP microarray was 95% concordant with conventional testing (39/41). Interestingly, 21% of patients (9/42) had fibroblast growth factor receptor 1 (FGFR1)amplification and had a 460% higher risk for mortality than those without FGFR1 amplification (p<0.01). In summary, MIP microarray provided a robust assessment of genomic CNA of breast cancer.

Bovine milk transcriptome analysis reveals microRNAs and RNU2 involved in mastitis

“…Bovine chromosome 19 is highly conserved relative to human chromosome 17 , and several well‐known human breast cancer‐related oncogenes and tumor‐suppressor genes, such as HER2 , TP53 , and BRCA1 , are located on chromosome 17 . Molecular genetic abnormalities on human chromosome 17, including monosomy or polysomy, have been observed in human breast cancers , and chromosome 17 and the HER2 locus are most frequently involved in chromothripsis‐like patterns in human breast cancer . BRCA1 mutations are associated with worse overall survival in women with breast cancer , and BRCA1 also affects resistance to bovine mastitis .…”

MET amplification assessed using optimized FISH reporting criteria predicts early distant metastasis in patients with non-small cell lung cancer

“…In addition, using our suggested reporting criteria, those cases with tumor cells with clustering MET -FISH signals in > 10% cells would be considered to be positive and this can be considered as alternative method to address tumor heterogeneity to at least some degree. To further address tumor heterogeneity, we recommend reflex testing by repeating FISH or reflex testing using alternative assays, such as chromogenic in situ hybridization [ 27 ], microarray-based technology [ 28 , 29 ], comprehensive molecular characterizations or sequencing based single cell analysis, etc. to accurately determine relevant copy numbers in cells with tumor heterogeneity as previously reported [ 1 , 2 , 30 ].…”

FGF‐2 and FGFR‐1 might be independent prognostic factors in oral tongue squamous cell carcinoma

“…Under homeostatic situations, fibroblast growth factor receptor (FGFR)‐1 is signalled by growth factors, such as FGF‐2 . Changes in the FGF‐2–FGFR‐1 pathway have been identified in several types of cancer, including non‐small‐cell lung cancer, breast cancer, oesophageal cancer, lymphoma, hepatocellular carcinoma, and glioblastoma . Although the roles of FGF‐2 and FGFR‐1 in OSCC tumorigenicity and metastasis progression have previously been investigated, mainly with experimental models, few studies have evaluated the impact of these markers on the outcome of patients with oral cancer …”