Prostate cancer is now the second leading cause of cancer in men, with recent genome-wide studies helping to clarify the genetic basis of this common but complex disease1. Many of these studies have reinforced the importance of homologous end repair genes including: ATM, BRCA1, BRCA2 and PALB2, in the mechanism of prostate cancer development. Mutations in these genes result in cells having to repair lesions through other non-conservative mutagenic mechanisms.
Choose your ideal prostate cancer NGS panel from our range of fully optimised NGS panel content. Simply mix and match the genes or individual exons you require and get the most out of your sequencing runs. Use in conjunction with the SureSeq™ FFPE DNA Repair Mix* for improved NGS library yields, %OTR (on target rate) and mean target coverage from challenging FFPE derived samples.
Getting started with your SureSeq myPanel™ NGS Custom Panel could not be simpler, find out more in this video…
* Exon examples not yet available
We have a regularly updated, expert-curated library of pre-optimised cancer panel content for you to select from. Simply mix and match the gene, exonic or intronic content you need to create a prostate cancer NGS cancer panel that meets your exact requirements.
A number of genetic factors have been found that increase prostate cancer risk, including heritable mutations in the genes BRCA1 and BRCA2. BRCA1 is a key player in cellular control systems, having been linked to DNA damage response and repair, transcriptional regulation and chromatin modelling2, while BRCA2 function is linked to DNA recombination and repair processes, being of particular importance in the regulation of RAD51 activity. Figure 1 illustrates the superior uniformity of coverage of key exons of BRCA1 and BRCA2 from an FFPE sample.
PALB2 is a BRCA2 binding protein and the BRCA2-PALB2 interaction is essential for BRCA2-mediated DNA repair. Recently it has been shown that correct PALB2 function is necessary for the homologous recombination repair via interaction with BRCA1, revealing that PALB2 is actually a linker between BRCA1 and BRCA23. The ATM gene, located on chromosome 11q 22–23, includes 66 exons with a 9168 base NGS Custom Prostate Cancer panel 3 pair coding sequence, and encodes a PI3K-related protein kinase (PIKK) that helps maintain genomic integrity. The PI3K-AKT-mTOR oncogenic pathway is frequently enhanced in prostate cancer playing a vital role in development and maintenance4. Figures 2 and 3 illustrate the excellent uniformity of coverage of key exons of PALB2 and ATM, respectively.
Figure 1a: BRCA1 exon 9 and 10 coverage. Depth of coverage per base (grey). Targeted region (green). Gene coding region as defined by RefSeq (blue). GC percentage (red).
Figure 1b: BRCA2 exon 11 coverage. Depth of coverage per base (grey). Targeted region (green). Gene coding region as defined by RefSeq (blue). GC percentage (red).
Figure 2a: Illustration of the excellent uniformity of coverage of PALB2 exon 5. Targeted region (green). Gene coding region as defined by RefSeq (blue). GC percentage (red).
Figure 2b: Illustration of the excellent uniformity of coverage of PALB2 exon 13. Targeted region (green). Gene coding region as defined by RefSeq (blue). GC percentage (red).
Figure 3a: Illustration of the excellent uniformity of coverage of ATM exon 45. Targeted region (green). Gene coding region as defined by RefSeq (blue). GC percentage (red).
We were delighted with the performance of the SureSeq panel. It showed complete concordance with our other techniques, detecting all known mutations with excellent sensitivity down to 1% [MAF (minor allele frequency)], including, in one case, a JAK2 V617F mutation which was not detected by ddPCR due to a second mutation under the primer. The panel also demonstrated mutations in other genes in samples with low level JAK2 V617F and good correlation between allele frequencies and quantitative analysis by ddPCR. We are planning to adopt the panel in the near future.
Dr Anna Skowronska
R&D Scientist, Haemato-Oncology Team, West Midlands Regional Genetics Laboratory, Birmingham Women’s NHS Foundation Trust, UK