| 1. |
- Blattner, Mirjam, et al.
(författare)
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SPOP Mutations in Prostate Cancer across Demographically Diverse Patient Cohorts
- 2014
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Ingår i: Neoplasia. - New York : Elsevier. - 1522-8002 .- 1476-5586. ; 16:1, s. 14-U34
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Recurrent mutations in the Speckle-Type POZ Protein (SPOP) gene occur in up to 15% of prostate cancers. However, the frequency and features of cancers with these mutations across different populations is unknown.OBJECTIVE: To investigate SPOP mutations across diverse cohorts and validate a series of assays employing high-resolution melting (HRM) analysis and Sanger sequencing for mutational analysis of formalin-fixed paraffin-embedded material.DESIGN, SETTING, AND PARTICIPANTS: 720 prostate cancer samples from six international cohorts spanning Caucasian, African American, and Asian patients, including both prostate-specific antigen-screened and unscreened populations, were screened for their SPOP mutation status. Status of SPOP was correlated to molecular features (ERG rearrangement, PTEN deletion, and CHD1 deletion) as well as clinical and pathologic features.RESULTS AND LIMITATIONS: Overall frequency of SPOP mutations was 8.1% (4.6% to 14.4%), SPOP mutation was inversely associated with ERG rearrangement (P < .01), and SPOP mutant (SPOPmut) cancers had higher rates of CHD1 deletions (P < .01). There were no significant differences in biochemical recurrence in SPOPmut cancers. Limitations of this study include missing mutational data due to sample quality and lack of power to identify a difference in clinical outcomes.CONCLUSION: SPOP is mutated in 4.6% to 14.4% of patients with prostate cancer across different ethnic and demographic backgrounds. There was no significant association between SPOP mutations with ethnicity, clinical, or pathologic parameters. Mutual exclusivity of SPOP mutation with ERG rearrangement as well as a high association with CHD1 deletion reinforces SPOP mutation as defining a distinct molecular subclass of prostate cancer.
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| 2. |
- Svensson, Maria A., 1980-, et al.
(författare)
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A Comparative Study of ERG Status Assessment on DNA, mRNA, and Protein Levels Using Unique Samples from a Swedish Biopsy Cohort
- 2014
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Ingår i: Applied immunohistochemistry & molecular morphology (Print). - : Lippincott Williams & Wilkins. - 1541-2016 .- 1533-4058. ; 22:2, s. 136-141
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Tidskriftsartikel (refereegranskat)abstract
- The ERG rearrangement is identified in approximately 50% of prostate cancer screened cohorts and is known to be highly specific. This genetic aberration, most commonly leading to the TMPRSS2-ERG fusion, but also SLC45A3-ERG or NDRG1-ERG fusions, all leading to an overexpression of a truncated ERG protein. Most studies have applied in situ hybridization (FISH) methods or mRNA-based assays to investigate the ERG status. Recently, studies showed that ERG protein levels assessed by ERG antibodies can be used as a surrogate marker for ERG rearrangement. In the current study, we investigate ERG status on a series of diagnostic biopsies using DNA-based, mRNA-based, and protein-based assays. We formally compared 3 assay results (ie, FISH, fusion mRNA, and immunohistochemistry) to identify which method could be most appropriate to use when having limited amount of tissue. ERG rearrangement was found in 56% of the cases. Comparing ERG rearrangement status by FISH with ERG overexpression and TMPRSS2-ERG fusion transcript we found 95.1% (154/162, Fisher exact test 9.50E-36) and 85.2% (138/162, Fisher exact test 7.26E-22) concordance, respectively. We show that the ERG antibody highly correlates with the ERG rearrangement with high sensitivity and specificity. We also identified the most common TMPRSS2-ERG isoform in the majority of ERG rearranged cases. These results provide compelling evidence that the ERG antibody can be used to further investigate the role of ERG in prostate cancer.
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