Journal Article Review Epublish
PubMed: 39596040 DOI: 10.3390/ijms252211968
Estimating the Number of Polygenic Diseases Among Six Mutually Exclusive Entities of Non-Tumors and Cancer.
Int J Mol Sci 25(22)
Authors: C I Edvard Smith, Jan A Burger, Rula Zain
Affiliations
- Department of Laboratory Medicine, Karolinska Institutet, ANA Futura, Alfred Nobels Allé 8 Floor 8, SE-141 52 Huddinge, Sweden.
- Karolinska ATMP Center, Karolinska Institutet, Karolinska University Hospital, SE-171 76 Stockholm, Sweden.
- Department of Infectious Diseases, Karolinska University Hospital, SE-141 86 Huddinge, Sweden.
- Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
- Centre for Rare Diseases, Department of Clinical Genetics, Karolinska University Hospital, SE-171 76 Stockholm, Sweden.
Abstract
In the era of precision medicine with increasing amounts of sequenced cancer and non-cancer genomes of different ancestries, we here enumerate the resulting polygenic disease entities. Based on the cell number status, we first identified six fundamental types of polygenic illnesses, five of which are non-cancerous. Like complex, non-tumor disorders, neoplasms normally carry alterations in multiple genes, including in 'Drivers' and 'Passengers'. However, tumors also lack certain genetic alterations/epigenetic changes, recently named 'Goners', which are toxic for the neoplasm and potentially constitute therapeutic targets. Drivers are considered essential for malignant transformation, whereas environmental influences vary considerably among both types of polygenic diseases. For each form, hyper-rare disorders, defined as affecting <1/10 individuals, likely represent the largest number of disease entities. Loss of tumor-suppressor genes exemplifies such a profoundly rare mutational event. For non-tumor, polygenic diseases, pathway-centered taxonomies seem preferable. This classification is not readily feasible in cancer, but the inclusion of Drivers and possibly also of epigenetic changes to the existing nomenclature might serve as initial steps in this direction. Based on the detailed genetic alterations, the number of polygenic diseases is essentially countless, but different forms of nosologies may be used to restrict the number.
MeSH
Genes, Neoplasms, Leukemia, Autoimmunity