## 3 Problems and Prospects of Genetic Analysis via Liquid Biopsies  
As the detection of molecular diagnostic markers and oncogene panel tests for nucleic acids derived from cancer cells have played an important role in cancer diagnosis, the quality of DNA and RNA must also be improved [120; 121]. The ability to extract nucleic acids from raw or frozen pathology specimens as well as DNA and RNA from FFPE stored for several years has advanced high-quality nucleic acid extraction techniques [120]. Despite the increasing usefulness of liquid biopsies, which perform genetic analyses using the nucleic acids derived from bodily fluid samples, such as urine, ascites, and pleural fluid, the principles and methods of analysis are less clear as a specialized genetic analysis technique, in the manner of a black box. However, the ability of pathologists to perform genetic analyses from the same perspective as immunohistochemical staining is an extremely important revolutionary diagnostic tool. In addition, it is now possible to detect free nucleic acids in liquid samples, whereas in the past genetic diagnosis was only possible by extracting nucleic acids from tissues or cells. Similarly, the ability to use genetic analysis to evaluate the expression levels of watch molecules such as miRNAs, which are considered important small RNAs and miRNA target molecules, is another important advantage of genetic analysis methods. Furthermore, it is highly useful to detect somatic gene mutations, which are expected to be used as molecular targeted therapy in tissues and as free nucleic acids in urine. Ideally, genetic analysis, including quantitative PCR and NGS, should be commonly used by pathologists, as it provides an opportunity to determine how histopathology can be related to genetic abnormalities and to increase the basis for diagnosis. To this end, it is necessary to devise various methods to extract high-quality nucleic acids from both tissues and cells, as well as from liquid specimens subjected to liquid biopsy. To accomplish this, methods for DNA and RNA extraction from FFPE for tissues and liquid-based cytology for cells have been investigated [120; 121; 122]. Although many nucleic-acid-based biomarkers have been discovered in research settings and presented from a functional analysis or clinical point of view, very few biomarkers in the field of urology are useful for companion diagnostics. In bladder cancer, the genetic damage caused by external factors, such as smoking and chemical substances, may be more problematic than various hereditary factors [58], and genomic analyses focusing on gene repair mechanisms will be useful to target sighting genes. For this purpose, it is important to extract sufficient amounts of nucleic acids and to maintain their quality. Although urine is a convenient specimen that can be obtained noninvasively, the problems of maintaining its quality and quantity must be solved. Single-nucleotide polymorphism-based oncogenes in bladder cancer include MYC, TP53, PSCA, TERT, FGFR3, TACC3, NAT2, CBX6, APOBEC3A, CCNE1, and UGT1A [124; 125; 126; 127]. These genes are involved in carcinogen detoxification, cell cycle regulation, and apoptosis, and their collective analysis has the potential to comprehensively detect risk factors with a genetic background; however, their therapeutic application is still under development [124; 125]. An alternative strategy would be to establish combinations of miRNAs involved in the function of these genes and then to build an algorithm for diagnosis. Prostate cancer progresses slowly and has a long course, which is highly stressful due to treatments such as brachytherapy, hormonal therapy, and chemotherapy, which may cause various genetic alterations. Therefore, it is important to understand the genetic changes and select treatments for castration-resistant and other treatment-resistant prostate cancers.