Hereditary renal cell carcinoma syndromes: diagnosis, surveillance and management

Abstract

Increasing knowledge of the natural history and genetic basis has led to characterisation and tailored management of hereditary RCC syndromes. International data sharing of inherited RCC gene variant information may enable evidence-based improvements in the diagnosis, surveillance protocols and management of these rare conditions.

WHO/ISUP classification, grading and pathological staging of renal cell carcinoma: standards and controversies

“…In 90% of cases, these tumours exhibit alterations in the von Hippel–Lindau tumour suppressor (VHL) gene on chromosome 3 [25]. Most tumours are sporadic, but multiple bilateral tumours are seen in von Hippel–Lindau syndrome, a rare autosomal dominant condition also associated with a variety of other tumours that include haemangioblastomas of the retina and central nervous system [26]. Multifocal sporadic tumours are rare and a recent study has shown that apparent multifocality may be due to retrograde venous invasion from a single tumour [27].…”

Genomics and clinical correlates of renal cell carcinoma

“…Genetic risk factors are known to play a role in sporadic RCC development [7, 8]. Patients who have at least one first degree relative with RCC are at an increased risk of developing the disease (OR 1.4, 95% CI 0.71–2.76) [9].…”

“…Signature 2, associated with APOBEC family of cytidine deaminases is the next most common signature. Classified as either type I or type II in roughly equal proportions, pRCC occurs either sporadically or as an inherited form [7]. In general, type I cancers are often multifocal and confer a better prognosis than the more aggressive and typically unifocal type II cancers [55].…”

“…Hereditary papillary renal cancer (HPRC) predisposes to type I pRCC via autosomal dominant inheritance of a mutation in the MET proto-oncogene [7]. Increased MET mRNA expression is commonly observed in the sporadic form of the disease [56].…”

“…The inherited form of the more aggressive, type II pRCC tumours is caused by germline mutation of the gene encoding fumarate hydratase (FH) [7]. Sporadic FH mutations are rarely found; however, mutations of genes in the downstream NRF2–antioxidant response element (ARE) pathway such as NFE2L2 are recurrently detected.…”