Cancer: the patient’s ‘genetic map’ aids treatment and also identifies risk genes

In 10 per cent of patients, there are genetic alterations that predispose them to cancer and which are also found in healthy cells; these alterations contribute to the development of tumours and may also be present in the patients’ family members. This is what researchers at the A. Gemelli University Polyclinic IRCCS Foundation have discovered by mapping the genetic profile of tumour cells in patients with solid tumours.

This is the result of research carried out as part of the FPG500 programme, strongly championed by Professor Giovanni Scambia, former Scientific Director of the Agostino Gemelli University Polyclinic IRCCS Foundation and, since 2022, based at the Gemelli, and led by researchers Simona Duranti, Arianna Panfili and Camilla Nero, and coordinated by Professor Maurizio Genuardi, Professor of Medical Genetics at the Università Cattolica del Sacro Cuore and Director of the Complex Operational Unit of Medical Genetics at the Agostino Gemelli University Polyclinic Foundation (IRCCS). This type of genomic analysis has made it possible to identify several patients carrying a hereditary syndrome that predisposes them to cancer, a third of whom would probably not have been identified through the standard diagnostic pathway. The study has just been published in the journal *Genome Medicine*.

In the study, genomic profiling of certain types of tumours was carried out using next-generation sequencing (NGS) of over 500 genes. In addition to identifying genetic variants acquired during the course of a person’s life that promote the development of cancer – which are useful in guiding the choice of the most effective treatment – it was also possible to identify alterations of a suspected constitutional nature, i.e. those present from birth in all the patient’s normal cells, affecting genes that are key to tumour development. Constitutional genetic alterations were present in one in ten patients. It can therefore be said that a genetically based predisposition to cancer was identified in one in ten patients.

In particular, during the first two years of the programme (January 2022 – December 2023), approximately 2,700 samples from patients with solid tumours were analysed, the majority of which were gynaecological tumours (endometrial and ovarian). Thanks to the integrated multidisciplinary work of several specialists, including molecular biologists, bioinformaticians, oncologists, geneticists and molecular care managers, 16 per cent of patients who underwent tumour profiling were referred for specialist assessment at the Medical Genetics outpatient clinic. The take-up rate for genetic consultations amongst those invited was 80 per cent.

Extensive tumour genomic profiling is recommended for the identification of ‘actionable’ mutations – those that may be targeted by treatment – in a subgroup of cancer patients. In Italia, the National Health Service reimburses tests for a limited number of genes, linked to specific drugs and cancers, such as lung, ovarian or colon cancer. The new Essential Levels of Care (LEA), which come into force on 30 October 2026, expand the range of reimbursed molecular tests, but these are panels targeted at a single cancer. ‘A test covering over 500 genes is not part of routine clinical practice,’ explain Drs Duranti and Panfili: ‘At Gemelli, it is offered as part of the FPG500 programme, which is both diagnostic and research-based.’