Human Cancer Genetics Programme

Familial Cancer Clinical Unit

Head of Unit:  Miguel Urioste
Research highlights

The FCCU maintains its engagement to enhance the comprehensive understanding of the principles of genetics in a clinical scenario. We maintain a narrow relationship with almost all of the professionals involved in hereditary cancer care in our country, as well as with SEOM and AEGH. We actively participate in general genetics courses, cancer susceptibility classes, seminars targeted at different clinical disciplines, etc., in hospitals from all over Spain, medical schools and other centres. The Cancer Genetics Consultancy in the Fuenlabrada University Hospital (HUF) enables us to offer a more integrated model of instruction, training future health-care providers through rotations in the Consultancy, and inviting them to participate in clinical sessions provided by the CNIO Human Genetics Programme and conducted by HUF’s Hereditary Cancer Clinical Committee. We have also continued the relationship with certain patient associations in order to circulate basic knowledge regarding cancer predisposition. We regularly participate in the annual meetings of different associations and have also initiated specific research collaborations with some of them.

Our clinical and diagnostic activities this year can be summarised as follows: 506 patients visited our consultancy at HUF (24.02% increase over 2016), and 428 genetic diagnostic studies were performed in the FCCU laboratory (21.59% increase). We are also currently working with a recently reviewed multigene panel that includes more than 90 cancer predisposition genes.

The FCCU actively contributes to the research on less frequent cancer predisposition syndromes. The PTEN hamartoma tumour syndrome (PHTS) collectively refers to several rare diseases with overlapping clinical features, a germline cause and an increased predisposition to various cancer types. Our study presents a series of 144 individuals of Spanish origin with PHTS in whom we interrogate the mutational and clinical spectra. Comparisons with respect to other population studies are discussed and guidelines for PHTS patient management are suggested. This is the largest study in Spanish PHTS patients. Our results are in agreement with previously published works in other populations, with a few exceptions such as a higher frequency of mutations in exon 1 (FIGURE). Finally, we discuss the usefulness of the diagnostic criteria established for this disease, based on our findings in the PTEN+ vs the PTEN- cohorts. A manuscript reporting all this information in detail is ready for submission. We are also working with the PTEN Research Foundation (UK) in order to increase awareness and diagnosis of PHTS and to build professional networks that facilitate advances in the understanding of the disease.

Our research in colorectal cancer (CRC) has continued to focus on early-onset forms of CRC (EOCRC). We have identified a recurrent deletion of 16p13.12-p13.11 chromosomal region in EOCRC. This deletion was associated with a better prognosis. The NOMO1 gene is located in this chromosomal region, and we also observed homozygous deletion of this gene mainly associated with EOCRC, and particularly with microsatellite stable subtypes. Our findings may serve as a starting point for further studies to confirm the potential carcinogenic value of this 16p13.12-p13.11 deletion, which would place NOMO1 in a suitable position as a potential therapeutic target for EOCRC treatment.