Effects of TET2 mutations on DNA methylation in chronic myelomonocytic leukemia

Figures & data

Figure 1 DNA methylation levels of AIM2 and SP140 in samples from patients with mutant and wild-type TET2. DNA methylation level of normal peripheral blood samples is shown in the light gray rectangle. MT, TET2 mutant cases; WT, wild-type cases.

Figure 2 5-methyl-cytosine levels in TET2 mutant and wild-type cases. 5-methyl-cytosine levels in genomic DNA (%) are measured by mass spectrometry in the samples where a sufficient amount of nucleic acids was available. MT, TET2 mutant cases; WT, wild-type cases.

Table 1 TET2 mutation status

Patient	Nucleotide change	Amino acid change
MT1	c.1623C > T	Q255X
MT2	Del c.3022_3023 (CA); Ins 4636 (GCTCA)	H721FS; T1259FS
MT3	c.2820C > T; c.4559C > A	Q654X; W1233X
MT4	c.4500C > T; c.5850C > T	R1214W†; Q1664X
MT5	c.6508C > T	T1883I
MT6	c.5163C > T	Q1435X*
MT7	Ins c.2617 (T); c.3869G > A; c.5469C > T	L586FS; W1003X; Q1537X†
MT8	c.4998C > T	H1380Y
MT9	Del c.3442 (A)	N861FS
MT10	Del c.5521_5524 (CAGA)	T1554FS†
MT11	c.4435G > T	G1192V
MT12	Ins c.2519 (G)	V553FS
MT13	c.6012G > T	V1718L†,§
MT14	c.4753G > A	C1298Y
MT15	Del c.2653 (A)	N598FS
MT16	c.5109G > T	V1417F*,†

* Biallelic/homozygous mutations;

† Previously reported;

§ Predicted to be tolerated.

Table 2 Patient characteristics

		TET2 mutant	TET2 wild type	p value
Total (n = 30)		16	14
Age (median, range)		71 (51–77)	75 (39–82)	0.40
Median survival (months)		10.4	12.2	0.71
Progression free survival (months)		10.4	11.0	0.75
Gender
	Male (%)	9 (56)	12 (86)	0.12
	Female (%)	7 (44)	2 (14)
Blood count mean
	Hb (g/dL)	11.1	8.8	0.01
	ANC (×10^9/L)	8.0	5.3	0.39
	Platelets (×10^9/L)	92.3	96.2	0.92
Bone marrow blasts (%)		7.8	10.7	0.23
Cytogenetic category
	Good (%)	12 (75)	11 (79)	1.00
	Intermediate (%)	4 (25)	3 (21)

ANC, absolute neutrophil count; Hb, hemoglobin.

Table 3 DNA methylation levels

		TET2 mutant (n = 16)			TET2 wild type (n = 14)			Normal peripheral blood (n = 5)			p value
			Range			Range			Range		(TET2 mutant vs. wild type)
Gene	CpG island	Median (%)	Min (%)	Max (%)	Median (%)	Min (%)	Max (%)	Median (%)	Min (%)	Max (%)
ER (ESR1)	Y	3	1	36	5	0	23	4	1	5	0.69
NOR1 (OSCP1)	Y	2	0	24	2	0	18	3	1	4	0.73
p15 (CDKN2B)	Y	7	0	29	8	2	15	3	1	7	0.76
NPM2	Y	6	1	17	7	0	14	3	2	4	0.68
ECAD (CDH1)	Y	5	2	31	10	2	39	7	6	9	0.25
CDH13	Y	14	0	29	16	3	43	6	4	8	0.27
OLIG2	Y	10	3	37	14	4	35	6	3	8	0.32
PGRB	Y	28	6	46	16	5	54	6	1	11	0.04
PGRA	Y	15	0	40	12	1	34	5	2	6	0.71
RIL (PDLIM4)	Y	19	8	68	28	5	68	21	12	33	0.56
C9orf16	Y	5	1	34	4	0	14	16	0	27	0.72
PSMD6	N	44	18	80	41	0	81	51	48	58	0.42
LRRC32	N	13	6	50	23	7	63	40	29	47	0.14
TMEM34	Y	22	2	42	13	1	68	16	8	22	0.33
FSD1NL	Y	7	2	35	7	3	50	34	25	61	0.56
AIM2	N	80	21	88	31	3	94	28	9	43	0.007
SP140	N	83	38	93	49	11	64	12	9	38	0.001*
ACOX3	Y	62	32	88	67	32	91	63	62	67	0.61
SLC39A14	N	89	8	99	94	28	100	95	76	100	1.00
ZNF662	Y	7	4	12	4	4	18	12	8	18	0.77
DNM3	N	2	1	5	3	1	9	4	3	6	0.80
LINE-1	N	86	78	92	83	78	88	81	75	84	0.23

* significant after Bonferonni's correction.