The emerging landscape of germline variants in urothelial carcinoma: Implications for genetic testing Journal Article
| Authors: | Vlachostergios, P. J.; Faltas, B. M.; Carlo, M. I.; Nassar, A. H.; Alaiwi, S. A.; Sonpavde, G. |
| Article Title: | The emerging landscape of germline variants in urothelial carcinoma: Implications for genetic testing |
| Abstract: | Urothelial carcinoma (UC) of the bladder and upper tract (ureter, renal pelvis) is one of the most frequently occurring malignancies. While the majority of UC are chemically induced by smoking, accumulating evidence from genetic studies have demonstrated a small, but consistent impact of heritable gene variants and family history of UC on the development of the disease. Beyond the established association between upper tract UC and germline mismatch DNA repair defects as a defining feature of Lynch syndrome, newer investigations focusing on moderate- and high-risk cancer-related gene variants in DNA damage repair and other signaling pathways are expanding our knowledge on the heritable genetic basis of UC, opening new avenues in the breadth of genetic testing and in clinical counseling of these patients. Overcoming existing challenges in the interpretation of uncertain findings and family cascade testing may help expand our testing approach and guidelines. Following the paradigm of other tumor types, such as breast and ovarian cancers, germline genetic testing, particularly when combined with somatic testing, has the potential to directly benefit affected UC patients and their families in the future through therapeutic targeting (i.e. with poly(ADP-ribose)) polymerase inhibitors, immune checkpoint inhibitors) and genetically informed screening/surveillance, respectively. © 2020 The Authors |
| Keywords: | immunohistochemistry; signal transduction; protein expression; single nucleotide polymorphism; cancer risk; polymerase chain reaction; rad50 protein; dna damage; gene; dna repair; computer assisted tomography; ovary cancer; prevalence; genotype; genome-wide association study; brca1 protein; brca2 protein; bladder cancer; protein p53; risk factor; messenger rna; urothelial carcinoma; atm protein; dna sequence; checkpoint kinase 2; epithelial cell adhesion molecule; genetic screening; transitional cell carcinoma; lynch syndrome; mismatch repair protein; protein msh6; mismatch repair protein pms2; genetic testing; hereditary nonpolyposis colorectal cancer; cyclin h; non profit organization; programmed death 1 ligand 1; fanconi anemia group d2 protein; dna glycosylase muty; bap1 gene; xeroderma pigmentosum group d protein; human; priority journal; article; fancm gene; nbn gene; mutl protein homolog 1; dna mismatch repair protein msh2; ercc3 gene; genetic risk score; germline variants |
| Journal Title: | Cancer Treatment and Research Communications |
| Volume: | 23 |
| ISSN: | 2468-2942 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2020-01-01 |
| Start Page: | 100165 |
| Language: | English |
| DOI: | 10.1016/j.ctarc.2020.100165 |
| PROVIDER: | scopus |
| PUBMED: | 31982787 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
