**9. Future perspectives**

The contents of routine gene panels are based on the knowledge on kidney cancer susceptibility genes. If a patient's DNA sequencing has failed to identify the hereditary mutation, RNA sequencing may identify the specific diagnosis [57]. If there are three patients in the family, trio exome analysis may be a pivotal method. Potentially, tumor tissue-only test would be a useful method to find out novel kidney cancer susceptibility genes and mutations in kidney cancer patients, as the knowledge on hereditary kidney cancer genes is still limited. This investigation is not available currently.

Tumor tissue-only gene tests by next generation sequencing with targeted genes may be soon routinely used for cancer patients' pharmacogenetic genotyping and analyzing their tumor tissue's somatic mutations to tailor their medical treatment [58]. The same method could be also a first step analysis for identifying the hereditary cancer mutation in a gene that is known in literature as a susceptibility gene. An additional test of patient's peripheral lymphocyte should then be used to confirm the susceptive mutation as hereditary mutation.

The growing knowledge on the biology of hereditary kidney cancer produces information about driver genes in kidney cancer tumorigenesis and may develop diagnostics and therapeutic methods for kidney cancer in general [59]. Knowledge on evidence-based medicine in metastatic hereditary kidney cancer [60] is under active study. Analysis of induced pluripotent stem cells (iPSC) from HPRC pointed that drug screening and precision medicine are possible for hereditary kidney cancer [61]. Preventive medicine may be achieved for healthy persons with familial mutation predisposing to kidney cancer [61].

Prospective studies about the method of follow-up in healthy persons with family kidney cancer susceptibility mutation are warranted. The optimal onset to start follow-up in *FH*related hereditary kidney cancer families should be clarified as currently there is no consensus. It is known that the prognosis in early-stage kidney cancer disease is better than in later stages [62]. Studies about long-term effect of surveillance in healthy carriers in hereditary kidney cancer families are needed. Additionally, further research is needed to understand the actual impact of genetic testing on young family members [63].
