15 General introduction biopsies showed the same mutations (57). The presence of tumor-derived DNA in the urine offers opportunities for urine-based cancer detection (58). 1.4 Urine as a liquid biopsy Urine is a relatively new liquid biopsy as compared to blood. Even though blood-based cancer detection methods have shown high clinical potential, particularly for their use in diagnostics and treatment response monitoring (59, 60), this method comes with several drawbacks. The collection of blood mostly requires in-person visits and is usually performed by a specialist. Moreover, only limited amounts of blood can be collected per time point. Urine, on the other hand, is truly non-invasive and can be collected easily, repeatedly, and in large volumes without pain or discomfort. The noninvasive nature of urine sampling allows for self-collection at home with high patient acceptance (61). Urine is a dynamic fluid that consists of a variety of components (Figure 3). Nucleic acids found in the urine can be broadly classified into a high and low molecular weight group. The high molecular weight DNA (≥1 kb in size) is derived from cellular debris, such as immune cells and exfoliated cells from the genital tract or distal urethra (62). The low molecular weight DNA (10-250 bp in size) comprises small transrenally excreted fragments (63). Full void urine contains both high and low molecular weight DNA, which can be divided by separating the urine into two fractions: the urine sediment and the urine supernatant. The urine supernatant is enriched for cfDNA (low molecular weight DNA), while the urine sediment mostly contains cellular debris (high molecular weight DNA). The most optimal urine fraction may depend on the location of the tumor. For example, the urine sediment was shown to be most optimal for detecting bladder and cervical cancer, as this fraction most likely contains the highest yield of exfoliated cancer cells (64, 65). Urine has been primarily explored as a liquid biopsy for urogenital cancer types that directly release DNA fragments into the urine, including bladder and cervical cancer (22, 65-70). In recent years, there has been growing interest in the detection of nonurogenital cancers in urine in which direct shedding is unlikely (62, 71). The transrenal excretion of tumor-derived cfDNA offers opportunities for the detection of virtually any cancer type that releases cfDNA into the bloodstream (57). Even for cancer types close to the bladder and urethra (i.e. bladder and cervical cancer), both locally and transrenally released tumor-derived (cf)DNA add to the total bulk of DNA in the urine (72). Hence, urine holds the potential to become a universal tool to diagnose and monitor various cancer types (71). 1
RkJQdWJsaXNoZXIy MjY0ODMw