Clinical Research Programme

Molecular Diagnostics Unit

Head of Unit:  Luís Lombardía
Research highlights
Strengthening our support

During 2016, our catalogue has grown with the addition of a new molecular diagnostics test based on the detection, by bi-directional Sanger sequencing, of mutations in exons 4 and 5 of the MYD88 gene. Waldenström’s macroglobulinemia (WM) is a rare form of blood cancer that is characterised by an excess of malignant white blood cells (lymphoplasmacytic cells) in the bone marrow. It has been shown that WM is the result of a multistep transformation process that accumulates sequential oncogenic alterations. The most prominent is the L265P somatic activating mutation in the MYD88 gene (present in 90% of WM). Hence, its detection would enable us to differentiate WM (but also diffuse large B-cell vitreoretinal lymphoma or marginal zone lymphomas) from indolent B-cell or other chronic lymphoproliferative disorders.

Additionally, because identification of several gene alterations involved in the onset of myeloproliferative neoplasms (MPNs) has revealed the huge complexity of these diseases and has challenged their accurate differential diagnosis, we started working on the implementation and validation of a new assay that will enable us to detect mutations in the TET2 gene; this will complement the diagnosis of MPNs patients. Mutations in this tumour suppressor gene (present in 13% of MPNs) lead to genomic instability via epigenetic modifications and foster cancer progression. Recent studies have revealed that the order in which these mutations are acquired is critical. Thus, patients with early mutations in TET2 were more likely to have better prognosis compared to patients who had previous mutations in others genes linked to MPNs (FIGURE).

Lastly, we have completed the initial experimental phase of a clinical trial sub project, FRAGANCE, led by the CNIO Gastrointestinal Cancer Clinical Research Unit, which is geared towards precision medicine for fragile patients with advanced pancreatic cancer.


MDU has also upheld its policy regarding training programmes in 2016 by welcoming one medical resident and one undergraduate student.