Maira had required close medical surveillance for years because she was developing multiple polyps in her colon. Her mother and sister had faced a similar situation, to the extent that they eventually underwent colectomies because the number of polyps had become too difficult to manage through regular monitoring alone. Moreover, the risk of one or more of these polyps progressing to cancer was too high. Everything pointed to a genetic cause for this polyposis, but the specific mutation had not yet been identified. That changed when they came to Bellvitge. At REMMA Bellvitge, the Hereditary cancer research group has long been carrying out cutting-edge research into the genetic causes of hereditary tumours that affect entire families.
In patients with familial adenomatous polyposis, the recurrent development of colon polyps is a defining feature, carrying a high risk of colorectal cancer if not properly monitored. Most cases are linked to alterations in the APC gene. However, in Maira’s family, the specific variant identified had not yet been classified as disease-causing. This meant that there was strong suspicion, but no definitive answer to confirm the diagnosis.
In hereditary cancer, this distinction is crucial: as long as it remains unknown whether a genetic variant is truly pathogenic, it cannot be used with complete confidence to guide clinical surveillance within a family or determine which relatives require intensive screening and which do not.
A diagnosis for the entire family
Maira’s case was included in the IMPaCT-VUSCan project, a national initiative led by IDIBELL that studies families with suspected hereditary cancer predisposition. As Dr Conxi Lázaro, co-leader of the Hereditary Cancer Research Group at IDIBELL and ICO and promoter of the project, explains: “IMPaCT-VUSCan focuses on what are known as variants of uncertain significance (VUS), genetic alterations for which it is still unclear whether they are benign or whether they may be responsible for disease. To resolve this, the project combines bioinformatics tools, which help prioritise the most relevant variants, with laboratory experiments to assess the actual effects of the mutation.”
In Maira’s family, this process enabled researchers to study a specific variant in the APC gene that had not previously been analysed. The study demonstrated that the variant was indeed pathogenic, meaning it was the genetic cause of polyposis in the family. “We have finally been able to put a name and a cause to our disease, and thanks to that, everything is much clearer now,” says Maira.
Having a definitive genetic diagnosis also provides invaluable information for her children and other relatives. From now on, a genetic test can determine whether they have inherited the pathogenic variant identified in the family. Those who are not carriers can avoid unnecessary annual colonoscopies, while those who are carriers can benefit from closer monitoring, with prevention and early detection measures tailored to their level of risk.
Collaborative research to bring answers closer
Dr. Conxi Lázaro and the Hereditary Cancer Group within REMMA Bellvitge work closely with hospitals, laboratories and research centres across Spain to bring the most advanced genomic research to as many families as possible. The IMPaCT-VUSCan project brings together hereditary cancer clinical teams, bioinformatics groups and laboratories that work collaboratively to transform uncertain genetic variants into clinically meaningful answers.
This model is particularly important for rare and hereditary diseases, where each family may carry a unique or extremely uncommon genetic variant. Progress requires combining data, expertise and experience from multiple teams across a wide geographical area. In Maira’s case, a clinical suspicion first identified during a consultation progressed through genomic analysis, bioinformatics and laboratory-based functional validation, before returning to the family in the form of a diagnosis, prevention strategies and support.
Researching unique challenges together
Familial adenomatous polyposis is one of the more than 400 rare adult-onset diseases studied by REMMA Bellvitge, a programme promoted by IDIBELL at the Bellvitge Health Campus and the first in Spain dedicated specifically to these conditions. Bellvitge is a leading centre for rare diseases in adults thanks to its concentration of expertise, multidisciplinary coordination, broad territorial reach, and the integration of clinical practice and laboratory research within the same campus.
In these conditions, every case represents a complex and unique challenge that can only be addressed through a diverse and comprehensive approach. To accelerate diagnosis, discover new treatments and provide better support to patients, at REMMA Bellvitge we investigate unique challenges together.