Genetic testing in Urology, When & what?

There is a paradigm shift in the management of uro-oncology in recent years by the integration of genetic testing into routine clinical practice. As the knowledge of germline and somatic mutations enhances, genetic profiling is influencing the cancer screening, treatment selection and family risk assessment in ways that were once inconceivable.(1,2) Broadly, genetic mutations are divided into germline and somatic mutations.

Prostate cancer
Germline mutation testing	Somatic mutation testing
Indications Personal history of primary cancer diagnosis in organs other than prostate. Family history of PC diagnosed  ≤ 60 or  death in parents, siblings. Family history of breast cancer, colorectal cancer, or endometrial cancer diagnosed ≤  50 in parents, siblings or any age diagnosis of ovarian cancer, pancreatic cancer, metastatic PC. Family history of ≥ 2 cases of breast cancer or PC in parents, siblings or blood relatives, excluding the individual. Presence of metastatic PC, regardless of resistance status.$ High-risk localized PC. Intraductal or cribriform histology detected in localized PC.
To identify  Hereditary breast/ovarian cancer syndrome (BRCA1, BRCA2). Lynch syndrome (MLH1, MSH2, MSH6, PMS2, EPCAM). For Confirmation of the potential use of  PARP inhibitors and platinum-based chemotherapy in mPC (BRCA1, BRCA2). Pembrolizumab in mPC (MLH1, MSH2, MSH6, PMS2).	Genes Analysed Somatic cell mutations in mCRPC (AR, FOXA1, SPOP). Poor response to first-line NHA treatment in mCRPC with somatic cell mutations (CDKN1B, CDKN2A , CDKN2B , KRAS , PTEN , RB1 , SMAD4 , TP53 ).

Renal cell cancer
Germline mutation testing	Somatic mutation testing
Indications Bilateral or multiple renal masses.  Diagnosed at ≤ 46 years old.  ≥1 first- or second-degree relatives with RCC	Indications Stage 3 or 4 RCC
Genes Analysed VHL (Clear cell RCC) MET (hereditary papillary RCC) FLCN (Birt -Hogg-Dube Syndrome) TSC1, TSC2 (tuberous sclerosis complex) FH (hereditary leiomyomatosis renal cell carcinoma) BAP1 (BAP1 tumor predisposition syndrome) SDHA, SDHB, SDHC, SDHD (hereditary paraganglioma/pheochromocytoma syndrome) PTEN (Cowden syndrome) MITF (MITF cancer syndrome)	Genes Analysed Genetic indicator of immune checkpoint inhibitor (ICI) responsiveness, such as anti-PD1 inhibitors (PBRM1, MSH2, MSH6, CHEK2, ATM). Genetic indicator of MET gene TKIs (MET). Treatment outcome predictor for TKIs or ICI (PTEN, TP53, CDKN2A)

by Dr M Shazib Faridi, Baba Saheb Ambedkar Hospital, New Delhi