Somatic mutations in FAT cadherin family members constitute an underrecognized subtype of colorectal adenocarcinoma with unique clinicopathologic features

Table 1 Clinicodemographics and histologic features in 526 patients with colorectal adenocarcinoma (PanCancer Atlas)

Feature	Level	Number	MSS number
Age (yr), mean ± SD		65.8 ± 13.0	65.4 ± 12.7
Gender	Female	252 (47.9%)	218 (47.1%)
	Male	272 (51.7%)	243 (52.5%)
	Unknown	2 (0.4%)	2 (0.4%)
Histopathologic differentiation	Well	19 (3.6%)	18 (3.9%)
	Moderate	381 (72.4%)	351 (75.8%)
	Poor	114 (21.7%)	83 (17.9%)
	Unknown	12 (2.3%)	11 (2.4%)
Tumor location	Left	254 (48.3%)	248 (53.6%)
	Right	197 (37.5%)	149 (32.2%)
	Left and right	3 (0.6%)	3 (6.5%)
	Unknown	72 (13.7%)	63 (13.6%)
Tumor staging (pT)	T1	18 (3.4%)	17 (3.7%)
	T2	94 (17.9%)	83 (17.9%)
	T3	355 (67.5%)	310 (67.0%)
	T4	57 (10.8%)	52 (11.2%)
	TX	2 (0.4%)	2 (0.4%)
Nodal staging (pN)	N0	305 (58.0%)	255 (55.1%)
	N1	128 (24.3%)	120 (25.9%)
	N2	90 (17.1%)	85 (18.4%)
	NX	3 (0.6%)	3 (6.5%)
Metastasis (pM)	M0	388 (73.8%)	338 (73.0%)
	M1	68 (12.9%)	66 (14.3%)
	MX	70 (13.3%)	59 (12.7%)
Lymphovascular invasion	Present	178 (33.8%)	157 (33.9%)
	Absent	230 (43.7%)	202 (43.6%)
	Unknown	118 (22.4%)	104 (22.5%)
Ethnicity	Caucasian	273 (51.9%)	236 (51.0%)
	African-American	60 (11.4%)	51 (11.0%)
	Asian	12 (2.3%)	11 (2.4%)
	Unknown	181 (34.4%)	165 (35.6%)
Subtype	CIN	328 (62.4%)
	MSI	63 (12.0%)
	GS	58 (11.0%)
	POLE	10 (1.9%)
	Unknown	57 (10.8%)
Total		526	463

CIN: Chromosomal instability; MSI: Microsatellite instability; GS: Genomically stable; POLE: Polymerase epsilon mutation; MSS: Microsatellite stable.

Table 2 Genetic mutation types and numbers in FAT family genes in colorectal adenocarcinoma (PanCancer Atlas)

Gene	Missense mutation	Nonsense mutation	Splicing mutation	Frame shift deletion	Frame shift insertion	Inflame deletion	Total mutation	Mutation in Cadherin domains
FAT1	85	5	2	3	2	1	98	48 (49.0%)
FAT2	90	2	3	5	1	0	101	64 (63.4%)
FAT3	124	6	0	5	2	0	137	55 (40.1%)
FAT4	198	19	0	10	4	0	230	133 (57.8%)

Table 3 Association of clinicopathologic features with FAT somatic mutations in colorectal adenocarcinoma (PanCancer Atlas)

Clinicopathologic features	Mutated FAT genes	Wildtype FAT genes	P value	Mutated FAT genes (MSS)	Wildtype FAT genes (MSS)	P value
Mean age (mean ± SD)	66.5 ± 12.9	65.3 ± 13.0	0.912	65.6 ± 12.1	65.3 ± 12.9
Sex			0.689			0.825
Female	98 (49.0%)	154 (47.2%)		67 (46.5%)	151 (47.3%)
Male	102 (51.0%)	170 (52.1%)		77 (53.5%)	166 (52.0%)
Location			< 0.001a			0.038a
Left side	65 (32.5%)	181 (55.5%)		70 (48.6%)	178 (55.8%)
Right side	102 (51.0)	98 (30.1%)		57 (39.6%)	92 (28.8%)
pT stage			0.093			0.083
pT1-2	50 (25.0%)	61 (18.7%)		38 (26.4%)	61 (19.1%)
pT3-4	150 (75.0%)	263 (80.7%)		106 (73.6%)	256 (80.3%)
pN stage			0.005a			0.079
pN0	133 (66.5%)	172 (52.8%)		87 (60.4%)	168 (52.7%)
pN1	44 (22.0%)	84 (25.8%)		39 (27.1%)	81 (25.4%)
pN2	23 (11.5%)	67 (20.6%)		18 (12.5%)	67 (21.0%)
pM stage			0.006a			0.038a
pM0	153 (76.5%)	235 (72.1%)		110 (76.4%)	228 (71.5%)
pM1	15 (7.5%)	53 (16.3%)		13 (9.0%)	53 (16.6%)
Differentiation grade			0.332			0.172
G1-2	145 (72.5%)	255 (78.2%)		117 (81.3%)	252 (79.0%)
G3	47 (23.5%)	67 (20.6%)		20 (13.9%)	63 (19.7%)
Subtype			< 0.001a
CIN	92 (46.0%)	236 (72.4%)
MSI	56 (28.0%)	7 (2.1%)
GS	25 (12.5%)	33 (10.1%)
Lymphovascular invasion			0.313			0.516
Positive	61 (30.5%)	117 (35.9%)		44 (30.6%)	113 (35.4%)
Negative	90 (45.0%)	140 (42.9%)		63 (43.8%)	139 (43.6%)
Total	200 (38.0%)	326 (62.0%)		144 (31.1%)	319 (68.9%)

^aP < 0.05.

CIN: Chromosomal instability; MSI: Microsatellite instability; GS: Genomically stable; MSS: Microsatellite stable.