(a).

Chromosome	Type of genetic alteration	Candidate gene	Incidence	Function of protein	Prognosis
3p25-26	LOH, hypermethylation, mutations	VHL	Found in 57–91% of tumours [30, 31, 37, 40, 163–165]	pVHL targets HIFa degradation; nonfunctioning pVHL does not degrade HIFa leading to angiogenesis	No clear association between VHL status and tumour grade and stage or survival of patients [31, 36–38, 40, 165]
3p14.2	LOH, translocation, hypermethylation	FHIT  contains chromosome fragile site FRA3B	Aberrations in 69–90% of ccRCC [62, 64, 78, 166]; 51–90% of ccRCCs showed reduced or absent FHIT protein expression [72, 74, 77]	FHIT protein is involved in apoptosis and proliferation [167–170]	FHIT loss, an early event in RCC; correlation of inactivation with lower grade and stage as well as better survival [73, 74, 77, 78]
3p21.3	Hypermethylation	RASSF1A	Methylation in 23–91% ccRCC tumours [88, 171]	RASSF1A promotes cell cycle arrest, apoptosis, and microtubule stability [79]	Hypermethylation of the RASSF1A promoter is significantly associated with advanced stage, grade, and worse cancer specific survival [85, 86]; loss of RASS1A protein is found in most ccRCC; but tumours with RASSF1A immunopositivity associated with higher stage, grade, and worse survival [87]
3p21	Truncating and missense mutations	PBRM1	Mutations in 29–41% of ccRCC tumours [90, 92, 105, 109]	BAF180 subunit of the SWI/SNF (switch and sucrose nonfermentable) chromatin remodeling complex; SWI/SNF complex regulates cell differentiation, proliferation, replication, transcriptional regulation, and DNA repair [90, 172, 173]	Due to contradictory findings, relationship of PBRM1 status and prognosis is still unclear [103–106]
1p36.11	Copy number loss	ARID1A	Copy number loss in 16% of patients with ccRCC [93]	BAF250a subunit of SWI/SNF complex	Low ARID1A mRNA and BAF250a immunostaining associated with higher stage, grade, and worse disease-free and disease specific survival [93, 111]
3p21.3	Truncating and missense mutations	BAP1	Inactivated in 6–15% of ccRCC [91, 92, 105, 109]	BAP1 is involved in cell cycle regulation [174]	BAP1 is an indicator of worse prognosis [91, 105, 107–110]
3p21.31	Truncating and missense mutations	SETD2	Mutation in 8–16% of tumours [92, 105, 109]	SETD2 is a histone methyltransferase controlling transcriptional regulation [175]	SETD2 mutation associated with worse disease specific survival [105]
Xp11.2	Truncating and missense mutations	KDM5C	Mutation in 4–8% of tumours [92, 109]	Histone demethylase, transcriptional regulation [176]	Tumours with mutations in BAP1, SETD2, or KDM5C are significantly associated with higher stage [92]
5q21.2~q21.3	Copy number loss or gain	NA	Copy number gain in 32–34% and loss in 52–56.2% of tumours [112, 113]	NA	Significant association of loss at 5q21.2~q21.3 with high grade tumours in patients with 3p loss [113]
5q22~q23	Copy number loss or gain	NA	Gains in 48–52.4% and loss in 42.9–46% of tumours [112, 113]	NA	Gain at 5q22.3~q23.2 associated with smaller, low grade tumours and better disease specific survival; loss at 5q22.3~q23.2 significantly related to larger, high grade tumours and poor disease specific survival [112, 113]
5q31–qter	Copy number gain	NA	Gain in of 56.8% ccRCCs [112]	NA	Gain of 5q31–qter had better overall survival compared with patients without gain of 5q [114]
8p	LOH	NA	LOH in 32-33% of RCC tissue specimen [115, 116, 177]	NA	LOH on chromosomes 8p and 9p, a significant predictor of recurrence [115]; LOH of 8p correlated with higher stage and grade [116]
9p	LOH	Possible candidate gene at 9p21 CDK2NA/ARF [118, 119]	LOH in 14–33% of RCC tissue specimen [115, 117, 119]	p16 is the protein product of CDK2NA which regulates cell cycle [118, 119]	Associated with high grade and stage, lymph node involvement, metastases, recurrence, and worse survival [115, 117–120]
14q	LOH	Possible HIF1A at 14q23.2 [121]	Loss in 38–55% of tumours [116, 121, 178, 179]	HIF1a is a transcription factor which regulates cellular response during hypoxia, for example, angiogenesis	Correlation of LOH at 14q with advanced stage, grade, larger tumour size, recurrence, and shorter cancer specific survival [116, 121, 178–180]
Chromosome 7	Polysomy	NA	Polysomy 7 in 9.5–56.2% ccRCC [133, 181]	NA	Polysomy 7 associated with higher tumour grade, stage, and higher proliferative rate [133]

NA indicates not available.