The mutational frequency of BRAF and KRAS in low-grade serous testicular neoplasms-a case series.

AIMS: Low-grade serous neoplasms of the testis are rare neoplasms that show striking morphological similarities with the better-understood ovarian neoplasms. This study is to see if there are similar molecular abnormalities in these two tumours. The cell of origin, relationship with serous ovarian tumour and the pathogenesis of these neoplasms are not fully established. METHODS AND RESULTS: As low-grade serous ovarian neoplasms are known to harbour mutations in the MAPK pathway, we investigated the involvement of BRAF and KRAS mutations in low-grade testicular serous tumour by performing mutational analysis of seven cases. Mutational analysis was performed by melting curve analysis followed by bidirectional sequencing. Our findings showed BRAF and/or KRAS mutations in three of the seven cases, which is similar to the proportions reported in low-grade ovarian serous neoplasms. Of these three cases, one showed co-mutation of BRAF and KRAS. CONCLUSION: The findings of this study are in support of a role of aberrant signalling of the MAPK pathway in the pathogenesis of low-grade serous testicular neoplasms, and provide a genetic link between low-grade testicular and ovarian serous tumours.

Molecular diagnosis of the myeloproliferative neoplasms: UK guidelines for the detection of JAK2 V617F and other relevant mutations.

Molecular genetic assays for the detection of the JAK2 V617F (c.1849G>T) and other pathogenetic mutations within JAK2 exon 12 and MPL exon 10 are part of the routine diagnostic workup for patients presenting with erythrocytosis, thrombocytosis or otherwise suspected to have a myeloproliferative neoplasm. A wide choice of techniques are available for the detection of these mutations, leading to potential difficulties for clinical laboratories in deciding upon the most appropriate assay, which can lead to problems with inter-laboratory standardization. Here, we discuss the most important issues for a clinical diagnostic laboratory in choosing a technique, particularly for detection of the JAK2 V617F mutation at diagnosis. The JAK2 V617F detection assay should be both specific and sensitive enough to detect a mutant allele burden as low as 1-3%. Indeed, the use of sensitive assays increases the detection rate of the JAK2 V617F mutation within myeloproliferative neoplasms. Given their diagnostic relevance, it is also beneficial and relatively straightforward to screen JAK2 V617F negative patients for JAK2 exon 12 mutations (in the case of erythrocytosis) or MPL exon 10 mutations (thrombocytosis or myelofibrosis) using appropriate assays. Molecular results should be considered in the context of clinical findings and other haematological or laboratory results.

Guidelines for the measurement of BCR-ABL1 transcripts in chronic myeloid leukaemia.

Molecular testing for the BCR-ABL1 fusion gene by real time quantitative polymerase chain reaction (RT-qPCR) is the most sensitive routine approach for monitoring the response to therapy of patients with chronic myeloid leukaemia. In the context of tyrosine kinase inhibitor (TKI) therapy, the technique is most appropriate for patients who have achieved complete cytogenetic remission and can be used to define specific therapeutic milestones. To achieve this effectively, standardization of the laboratory procedures and the interpretation of results are essential. We present here consensus best practice guidelines for RT-qPCR testing, data interpretation and reporting that have been drawn up and agreed by a consortium of 21 testing laboratories in the United Kingdom and Ireland in accordance with the procedures of the UK Clinical Molecular Genetics Society.