Non-invasive detection of upper tract urothelial carcinomas through the analysis of driver gene mutations and aneuploidy in urine
Date Issued
2017-10
Author(s)
Springer, Simeon
Chen, Chung-Hsin
Li, Lu
Douville, Chris
Wang, Yuxuan
Cohen, Josh
Afsari, Bahman
Danilova, Ludmila
Silliman, Natalie
Schaeffer, Joy
Ptak, Janine
Dobbyn, Lisa
Papoli, Maria
Kinde, Isaac
Shun, Chia-Tung
Karchin, Rachel
Netto, George J.
Turesky, Robert J.
Yun, Byeong Hwa
Rosenquist, Thomas A.
Hruban, Ralph H.
Pu, Yeong-Shiau
Grollman, Arthur P.
Tomasetti, Cristian
Papadopoulos, Nickolas
Kinzler, Kenneth W.
Vogelstein, Bert
Dickman, Kathleen G.
Abstract
Abstract Upper tract urothelial carcinomas (UTUC) of the renal pelvis or ureter can be difficult to detect and challenging to diagnose. Here, we report the development and application of a non-invasive test for UTUC based on molecular analyses of DNA recovered from cells shed into the urine. The test, called UroSEEK, incorporates assays for mutations in eleven genes frequently mutated in urologic malignancies and for allelic imbalances on 39 chromosome arms. At least one genetic abnormality was detected in 75% of urinary cell samples from 56 UTUC patients but in only 0.5% of 188 samples from healthy individuals. The assay was considerably more sensitive than urine cytology, the current standard-of-care. UroSEEK therefore has the potential to be used for screening or to aid in diagnosis in patients at increased risk for UTUC, such as those exposed to herbal remedies containing the carcinogen aristolochic acid.
SDGs