The emerging landscape of germline variants in urothelial carcinoma: Implications for genetic testing

Cancer Treatment and Research Communications

Amin H. Nassar, M.D.¹  Maria I. Carlo, M.D.²  Guru Sonpavde, M.D.³  Sarah Abou Alaiwi, M.D.⁴  Panagiotis J. Vlachostergios, M.D., Ph.D.⁵  Bishoy M. Faltas, M.D.⁵ 

[1] Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, United States;Department of Cell and Developmental Biology, Weill Cornell Medicine, New York, NY, United States;Department of Medicine, Brigham and Women's Hospital, Boston, MA, United States;Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, United States;Division of Hematology and Medical Oncology, Weill Cornell Medicine, New York, NY, United States;

关键词: Bladder cancer;    Genetic testing;    Germline variants;    Urothelial carcinoma;    Lynch syndrome;   

DOI  :  

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown