Renal Cell Neoplasia Tables: Recurrent Cytogenomic Alterations

WHO Classification
Subtype	Clear Cell RCC	Papillary RCC Type 1	Papillary RCC Type 2 (heterogeneous group)	MiTF-Translocation RCC		Chromophobe RCC	Oncocytoma
Percentage	70-75%	15-20%	15-20%	1-5%		5%	5%
Origin	Proximal    Tubules					Collecting   Ducts
Copy Number Alterations [level of evidencea; clinical significanceb]
Whole genome		Mostly gains				Mostly losses	No CNAs (~50%) [1; R]
chr1	1p- (10%) [2; R]		1p- (25%) [2; R]	1p- (30%) [3; R]		-1 (90%) [1; D]c	-1/1p- soly (50%) [1; R]
chr2		+2 (18%) [2; R]				-2 (80%) [1; D]c
chr3	-3/3p- (VHL, KDM6A, KDM5C, SETD2, PBRM1) (90%) [1; D]	+3 (40%) [2; R]	3p-/cnLOH(3p) (21%) [2; R], 3p+ (12%) [3; R], 3q+ (21%) [3; R]			-3 (25%) [3; R]
chr4	4p- (10%) [2; R]		-4 (21%) [3; R]			+4 (10%) [3; R]
chr5	5p+ (24%) [2; R], 5q+ (SQSTM1) (40-60%) [2; R]		5q+/+5 (20%) [2; R]			-5 (25%) [3; R]
chr6	6q- (20%) [2; R]		-6 (17%) [3; R]	6p21 (TFEB) amp [2; D, P]		-6 (90%) [1; D]c
chr7	+7 (25%) [2; R]	+7/+7,+7 (84%) [1; D]c	+7 (25%) [1; D]	+7 (30%) [3; R]
chr8	8p- (25%) [2; R]		+8 (MYC) (10-33%) [3; R]			-8 (15%) [3; R]c
chr9	9p- (20%) [1; P] 9q- (20%) [2; R]		9p- (19%) [2; R], 9q- (17%) [3; R]	9p- (30%) [3; R]		-9 (35%) [3; R]
chr10	10q- (10%) [2; R]		10q- (17%) [3; R]			-10 (90%) [1; D]c
chr11			11q- (19%) [3; R]			-11 (10%) [3; R]
chr12	+12 (15%) [2; R]	+12 (52%) [2; R]	+12 (15%) [3; R]	+12 (35%) [3; R]
chr13		+13 (13%) [2; R]	-13 (20%) [3; R]			-13 (85%) [1; D]c
chr14	14q- (HIF1A) (40%) [1; P]		-14 (28%) [2; R]				-14 (10%) [2; R]
chr15			-15 (15%) [3; R]	-15 (15%) [3; R]
chr16	16p+ (12%) [2; R], 16q+ (10%) [2; R]	+16 (55%) [2; R]	16p+ (40%) [2; R], 16q+ (35%) [2; R]
chr17		+17 (84%) [1; D] c	17p- (8%) [3; R], +17/17q+ (50%) [1; D]	17p- (20%) [3; R], 17q+ (40%) [3; R]		-17 (90%) [1; D]c
chr18	-18 (10%) [2; R]		-18 (26%) [2; R]			-18 (15%) [3; R]
chr19
chr20	+20 (13%) [2; R]	+20 (40%) [2; R]
chr21			-21 (19%) [3; R]			-21 (70%) [1; D]c	-21 (15%) [3; R]
chr22			-22 (40%) [2; R]
X							-X (10%) [3;R]
Y							-Y (40%) [1; R with -1]c
Rearrangements [level of evidence; clinical significance]
	TERT promoter (5p15) (<10%) [3; R]			TFE3 (Xp11), TFEB (6p21) (100%) [1; D, P]		TERT promoter (5p15) (12%) [3; R]	CCND1 (11q13) (40%) [2; D]
Mutations (SNVs, Indels) [level of evidence; clinical significance]
Mutated in >20%	PBRM1 [2; R], VHL (also promoter methylation) [1; D]					TP53 [2; R]
Mutated in 10-20%	BAP1 [1; P], SETD2 [2; R]	MET [1; D]
Mutated in 5-10%	KDM5C, MTOR, PTEN, TP53 [2; R]		CDKN2A (also promoter hypermethylation) [2; P], MET [1; D]			PTEN [2; R]
Mutated in 2-5%	ARID1A, CDKN2A, KDMT2C/D, LRP1B, PIK3CA, PTEN, STAG2, TCEB1, TERT	CDKN2A/B, KDM6A, MLL3, NF2, NFE2L2, SMARCB1, TERT	BAP1, FAT1, KDM6A, NF2, NFE2L2, PBRM1, SETD2, STAG2, TERT, TP53			ARID1A, FAAH2, FAT1/4, FLT4, MICALCL, NIN, PDHB, PDXDC1, TSC1/TSC2, ZNF765	ERCC2, C2CD4C
Mitochondrial  DNA						MT-ND5 [3,D]	MT-COX1, MT-COX2, MT-COX3, MT-ND5, MT-CYTB [2,D]
Germline susceptibility
Germline susceptibility	§ mainly VHL (von Hippel-Lindau Syndrome) § PTEN (Cowden Syndrome) § FLCN (Birt-Hogg-Dube syndrome) § TSC1 and TSC2 (tuberous sclerosis) § SDHB (most common), SDHC (less common), SDHA (rare), SDHD (rare) (succinate dehydrogenase deficient RCC)	§ MET (Hereditary papillary RCC)	§ FH (Hereditary leiomyomatosis and RCC)		FCLN (Birt-Hogg-Dube syndrome)		FCLN (Birt-Hogg-Dube syndrome)
References	[9, 14, 17, 24, 27, 29, 32, 35, 49, 156-168]	[10, 42, 67-71, 73, 74, 98, 169-174]		[10, 121, 122, 124, 125, 175]	[11, 12, 103, 105, 106, 108, 109, 129, 137, 176, 177]		[12, 76, 102, 103, 105, 129, 132, 135-137, 140, 178-180]