- CDK12: an emerging therapeutic target for cancer. [Journal Article]
- JCJ Clin Pathol 2018 Aug 13
- Cyclin-dependent kinase 12 (CDK12) belongs to the cyclin-dependent kinase (CDK) family of serine/threonine protein kinases that regulate transcriptional and post-transcriptional processes, thereby mo...
Cyclin-dependent kinase 12 (CDK12) belongs to the cyclin-dependent kinase (CDK) family of serine/threonine protein kinases that regulate transcriptional and post-transcriptional processes, thereby modulating multiple cellular functions. Early studies characterised CDK12 as a transcriptional CDK that complexes with cyclin K to mediate gene transcription by phosphorylating RNA polymerase II. CDK12 has been demonstrated to specifically upregulate the expression of genes involved in response to DNA damage, stress and heat shock. More recent studies have implicated CDK12 in regulating mRNA splicing, 3' end processing, pre-replication complex assembly and genomic stability during embryonic development. Genomic alterations in CDK12 have been detected in oesophageal, stomach, breast, endometrial, uterine, ovarian, bladder, colorectal and pancreatic cancers, ranging from 5% to 15% of sequenced cases. An increasing number of studies point to CDK12 inhibition as an effective strategy to inhibit tumour growth, and synthetic lethal interactions have been described with MYC, EWS/FLI and PARP/CHK1 inhibition. Herein, we discuss the present literature on CDK12 in cell function and human cancer, highlighting important roles for CDK12 as a clinical biomarker for treatment response and potential as an effective therapeutic target.
- CD147 expression is associated with poor overall survival in chemotherapy treated triple-negative breast cancer. [Journal Article]
- JCJ Clin Pathol 2018 Aug 11
- CONCLUSIONS: CD147 is a putative marker in identifying TNBC or BLBC, and may be useful as a prognosis indicator for patients with TNBC or BLBC post chemotherapy.
- Many faces of the same myeloid neoplasm: a case of leukaemia cutis with mixed histiocytic and Langerhans cell differentiation. [Journal Article]
- JCJ Clin Pathol 2018 Aug 09
- Biomarkers for the diagnosis of venous thromboembolism: D-dimer, thrombin generation, procoagulant phospholipid and soluble P-selectin. [Journal Article]
- JCJ Clin Pathol 2018 Aug 09
- CONCLUSIONS: Our results confirmed D-dimer as the main biomarker of VTE and speculated a role for sP-selectin. The impact of thrombin generation was limited and no role emerged for the PPL clotting time. These observations need to be confirmed in large management studies.
- p16. [Journal Article]
- JCJ Clin Pathol 2018 Aug 03
- The p16 gene belongs to INK4 family of genes and is made up of four members: p16 INK4A , p15 INK4B , p18 INK4C and p19 INK4D , all of which share biological properties, namely, inhibition of c...
The p16 gene belongs to INK4 family of genes and is made up of four members: p16 INK4A , p15 INK4B , p18 INK4C and p19 INK4D , all of which share biological properties, namely, inhibition of cell growth and tumour suppression. After p53, p16 is the second most common tumour suppressor gene. It has been regarded as the familial melanoma gene. Immunohistochemistry for p16 has a well-defined role in distinct pathological scenarios. It is used to distinguish desmoplastic melanoma from reactive fibrous proliferation, with former showing strong nuclear positivity. In other types of melanoma, p16 protein expression is lost. Spitz nevi show retention of nuclear staining for p16. Benign mesothelial proliferations tend to retain nuclear p16 immunoreactivity, while malignant mesotheliomas lose expression. However, p16 fluorescent in-situ hybridisation analysis is recommended in the workup of malignant mesothelioma. Another common application of p16 immunohistochemistry is as an indicator for human papillomavirus (HPV) infection and p16 protein is overexpressed in HPV-associated tumours. In this context, p16 immunopositivity should be strong, diffuse, nuclear or nuclear and cytoplasmic in location. Another use for p16 is demonstration of p16 immunopositivity in well-differentiated and dedifferentiated liposarcoma.
- Review of diagnostic error in anatomical pathology and the role and value of second opinions in error prevention. [Journal Article]
- JCJ Clin Pathol 2018 Aug 01
- CONCLUSIONS: It was possible to ascertain that gynaecology, dermatopathology and gastrointestinal specimens had presented the greatest diagnostic challenge to the participant pathologists, determined as highest rate of diagnostic inaccuracy, that is, major discordance with respective case target diagnoses.Through a combination of routine second opinions, directed retrospective peer review and participation in appropriate external quality assurance schemes, the risk associated with these diagnoses can be minimised.
- Analysis of a large cohort of non-small cell lung cancers submitted for somatic variant analysis demonstrates that targeted next-generation sequencing is fit for purpose as a molecular diagnostic assay in routine practice. [Journal Article]
- JCJ Clin Pathol 2018 Jul 27
- CONCLUSIONS: A tNGS panel approach is practically achievable, with acceptable success rates and turnaround times, in the context of a routine clinical service. Furthermore, it provides additional clinically and analytically relevant information, which is not available from single gene testing alone.
- Eighth Edition Cancer Staging Manual of Breast Cancer by the American Joint Committee on Cancer: are the new changes to improve staging or a treatment decision tool? [Journal Article]
- JCJ Clin Pathol 2018 Jul 26
- Results of the UK NEQAS for Molecular Genetics reference sample analysis. [Journal Article]
- JCJ Clin Pathol 2018 Jul 20
- CONCLUSIONS: Over 100 laboratories took the opportunity to test the 'educational reference sample', showing a willingness to further validate their testing platforms. While it was encouraging to see that the most widely reported variants were those which should be included in routine testing panels, reporting of variants was potentially open to interpretation, thus clarity is still required on whether laboratories selectively reported variants, by either clinical relevance or variant frequency.
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- Correction: T cell clonality assessment: past, present and future. [Journal Article]
- JCJ Clin Pathol 2018; 71(7):660