Understanding the genetics of cancer in adolescents

As genetic analysis becomes cheaper and more widely available, oncologists are getting close to an era where tumour—somatic—and germline testing will form a greater component of the management of adolescents and young adults (AYA) with cancer. But before this can become common practice, more research is needed.

From the genomic profiling of tumours in this age group, although limited, it has emerged that cancers in AYA have fewer somatic mutations, the mutations are disease specific and only 30% of the significantly mutated genes overlap with those in adult pan-cancer analyses. In the ESMO–European Society of Paediatric Oncology (SIOPE) Collaborative Session, the up-to-date clinical implications of precision medicine will be presented, including measures to improve diagnosis (e.g., methylation profiling to characterise CNS tumours), the stratification of disease (e.g., medulloblastoma, acute lymphoblastic leukaemia) and treatment with molecular-targeted therapies (e.g., BRAF inhibitors in CNS tumours).

It has emerged recently that around 8% of paediatric patients and young adults with cancer have germline mutations in genes predisposing to cancer. Crucially, however, as we cannot identify those individuals by a family history of cancer, identification of these germline mutations is vital. We must remember that genomic analysis and genetic counselling go hand in hand, so, if we increase our use of genomic analysis, we will also need to make sure that we have enough trained healthcare cancer professionals in place to help these young patients understand their test result, treatment options and potential outcomes.

Precision medicine is the goal of genomic analysis and this targeted treatment approach has changed the landscape of treatment for adults. It should be the same for AYA but sadly, it is not. This is largely because of the outdated age limit criteria of the majority of clinical trials in Europe, which exclude a substantial proportion of our patients from studies of novel medicines. Efforts like the joint Innovative Therapies for Children with Cancer (ITCC)–SIOPE initiative, ACCELERATE Platform, are hoping to address this to some extent by strengthening international cooperation for drug development and by giving the opportunity of novel therapy to our patients who are not children but are not adults either. Also, the ESMO–SIOPE Cancer in AYA Working Group was formed 4 years ago with the main aim of promoting education about the unmet needs facing our AYA patients.

I think that, as a community, we must offer the best possible cancer care to every AYA with cancer. We need to find ways to obtain the resources and create the collaborations that will enable us to expand our understanding of the disease in this age group (including the genomic characterisation of their tumours) and provide better treatments to improve their outcomes.

This morning’s ESMO–SIOPE/AYA Collaborative Session, ‘Genetics and precision medicine for AYA with cancer’ (08.30 – 10.00, Salamanca Auditorium [Hall 3]) will discuss current knowledge in this area.