Clinical Research Programme

Molecular Diagnostics Unit

Head of Unit:  Luís Lombardía
Research highlights

During 2017, we completed the standardisation and implementation of a new assay, launched in 2016, which will enable us to detect mutations in exons 3, 6, 7, 9, 10 and 11 of the tumour suppressor gene TET2 and, therefore, enable a better prediction the prognosis of patients with myeloproliferative neoplasms.

We have also expanded our catalogue with the addition of 2 new molecular diagnostic tests based on bi-directional Sanger sequencing. The first one will enable the detection of activating mutations in exons 13, 14, and 22 to 28 of the proto-oncogene ERBB2 (Erb-B2 Receptor Tyrosine Kinase 2, aka HER2) in patients with breast, ovarian, colorectal, gastroesophageal and lung cancers. These oncogenic alterations can cause resistance to treatments with reversible tyrosine kinase inhibitors and, thus, promote a more aggressive and metastatic disease. Therefore, the detection of these mutations will significantly expand the range of patients that could benefit from useful targeted therapies (FIGURE).

The other assay will enable us to detect mutations in the POLE (Polymerase< Epsilon) gene. This gene codes for a DNA polymerase with a proofreading exonuclease activity, which thereby allows high-fidelity DNA replication to occur. Quite recently, a group of endometrial carcinomas (EC) − not sufficiently distinctive to allow accurate diagnosis based on routine histological staining − has been identified with a high rate of somatic missense point mutations, commonly reported at 3 hotspots in exons 9, 13 and 14 of POLE. These tumours are associated with improved progression-free-survival, which is not derived from a higher sensitivity to chemotherapy but are more likely linked to enhanced immunogenicity. Since the clinical praxis is to give adjuvant chemotherapy to most patients with EC, this test will enable us to avoid unnecessary treatments in POLE-mutated cancer patients.

Additionally, as in previous years, we continue to interact with national and international standardisation groups in order to maintain a high level of quality standards in the molecular diagnostic tests provided by us. Finally, we uphold our policy of welcoming clinicians and technical specialists in order to mentor and train them in the field.