Clinical genomics for “intractable diseases”
There are more than 340 diseases listed by the Japanese Ministry of Health, Labor and Welfare as “intractable diseases,” each with different causes. A major cause of these diseases is genetic abnormalities. In dominant inheritance, children typically develops the same disease as their parents, even if only one parent passes on a faulty gene. In recessive inheritance, a child typically develops a disease by inheriting a faulty gene from both parents. In this condition, the parents themselves basically do not appear to have the disease. Causative genes have been identified for many of these genetic disorders. Our hospital has provided genetic counseling to families affected by such disorders for many years.
Advances in genomic analysis technology have revealed new genetic abnormalities that were previously unknown. In addition, the pathogenesis caused by genetic abnormalities are being uncovered. For some diseases, treatments targeting these pathogenesis, such as oligonucleotide therapeutics, have been developed. These therapies have been applied to diseases such as Duchenne muscular dystrophy and spinal muscular atrophy, and these treatments are now widely available. In addition, a treatment for specific genetic mutations in amyotrophic lateral sclerosis has been approved overseas, and it is expected that this drug will soon be approved and available in Japan.
Preimplantation genetic testing (PGT) refers to genetic testing of embryos and selection of those without genetic abnormalities for implantation. Previously, PGT in Japan was generally limited to severe childhood-onset diseases, but has now been expanded to include adult-onset diseases.
It is becoming understood that multiple genes, rather than a single gene, contribute to disease susceptibility for many diseases. In the future, it is expected that information on disease susceptibility, drug efficacy, and the likelihood of side effects will be clarified, and that this information will be used to improve disease management (Fig.).
*Initiative on Rare and Undiagnosed Diseases（IRUD): a clinical research program as part of the rare/intractable disease project of Japan.
Clinical genomics for “cancer”
In recent years, the use of genomic information in cancer treatment has rapidly expanded. In hereditary cancers, genomic information is analyzed for the patients and their family members, enabling early diagnosis and risk assessment of cancer development. When another family member is diagnosed with cancer, this information plays a crucial role in selecting the appropriate treatment.
Cancer is no longer regarded simply as “uncontrolled cell growth in an organ,” but rather as a condition whose underlying mechanisms must be understood. Genomic information has become essential for understanding how cancer develops. Based on this information, highly effective new treatments are continuously being developed and available for various cancers.
Even in non-hereditary cancers, it has become clear that the accumulation of multiple genetic mutations can lead to cancer development. We can now select more effective treatments by identifying mutations in various genes.
Genetic mutations in cancer can be identified through “cancer multi-gene panel testing1.” However, due to the large number of mutations detected, it might sometimes be challenging to determine whether a mutation is associated with cancer development or not. At our Cancer Management Center, regular expert review meetings (Cancer Genome Expert Panels) are held to carefully evaluate the interpretation of gene mutations on a case-by-case approach. In addition, when a mutation related to hereditary cancer is found, the Hereditary Tumor Conference, regularly held at our Clinical Genomics Center, gathers specialists to discuss the findings in detail.
Thus, while cancer treatment based on genomic information offers significant advantages, it also requires a high level of expertise. In our hospital, Cancer Management Center and Clinical Genomics Center collaborate to provide advanced cancer clinical genomics.
- Cancer multi-gene panel testing examines genetic changes in cancer cells to understand the characteristics of cancer (see the article ” Cancer treatment evolving day by day“). ↩︎