Molecular approach to genetic and epigenetic pathogenesis of early-onset colorectal cancer

Table 1 MiRNA profile of lynch syndrome patients

MiRNA	Expression status	Function	Ref.
miR-155	Up	MMR deficiency	Valeri et al[46]
		MSI	Earle et al[48]
miR-26b	Down	MSS	Earle et al[48]
miR-31	Up	MSI	Earle et al[48]
miR-223	Up	MSI	Earle et al[48]
miR-486-5p	Down	MSI	Balaguer et al[47]
miR-622	Up	MSI	Balaguer et al[47]
miR-1238	Up	MSI	Balaguer et al[47]
miR-1362-5p	Down	MSI	Balaguer et al[47]
miR-132	Down	MMR deficiency	Kaur et al[49]
miR-345	Down	MMR deficiency	Kaur et al[49]

MSS: Microsatellite stabile; MSI: Microsatellite instability; MMR: Mismatch repair.

Table 2 Molecular characterization of familial colorectal cancer type X patients

Molecular features		Ref.
Germline MMR gene mutations	-	Lindor et al[51]
		Klarskov et al[52]
		Sánchez-Tomé et al[53]
Tumor supressor gene loci loss
APC mutations	77%	Francisco et al[56]
KRAS mutations	46%	Francisco et al[56]
MGMT methylation	36%	Francisco et al[56]
Chromosome gains	20q, 19 and 17	Therkildsen et al[57]
Chromosome loss	8p, 15, 18	Therkildsen et al[57]
Signaling by G protein coupled receptor	up-regulated	Dominguez-Valentin et al[58]
(GNAS, F2R, F2RL2, EDN1, EDNRA, GRM8, GNA2, GNG11, , HCRT, PTGER1, P2RY2, RAMP2, MC1R, TUBB3, VIP)
SEMA4A variants		Schulz et al[61]

Table 3 Genetic and epigenetic alterations of familial adenomatous polyposis patients besides adenomatous polyposis coli

		Alteration	Ref.
Gene
	GNAS	Mutation	Hashimoto et al[75]
	MYC	Gene activation	Obrador-Hevia et al[79]
	AXIN2	Gene activation	Obrador-Hevia et al[79]
	SFRP1	Gene activation	Obrador-Hevia et al[79]
	GSTT1	Polymorphism	Lamberti et al[74]
	MGMT	Methylation	Wynter et al[86]
	p14ARF	Methylation	Wynter et al[86]
	p16INK4	Methylation	Wynter et al[86]
	IGSF4	Methylation	Berkhout et al[85]
	TIMP3	Methylation	Berkhout et al[85]
	ESR1	Methylation	Berkhout et al[85]
	CDH13	Methylation	Berkhout et al[85]
miRNA
	miR-143	Down regulation	Kamatani et al[87]
	miR-145	Down regulation	Kamatani et al[87]
	miR-126	Down regulation	Yamaguchi et al[88]
	miR-20b	Down regulation	Yamaguchi et al[88]

Table 4 MUTYH mutations that vary with ethnicity

MUTYH mutation	Etnicity	Ref.
c.231 C > T	Japan	Miyaki et al[99]
c.934-2A > C	Japan	Miyaki et al[99]
c.1376C > A	Finland	Alhopuro et al[100]
c.933 + 3A > C	North-Eastern Italy, Germany	Pin et al[101]
c.536A > G	Caucasians	Yamaguchi et al[92]
c.1187 G > A	Caucasians	Yamaguchi et al[92]

Table 5 Pathogenic germline mutations of juvenile polyposis syndrome

Mutation	Effect	Ref.
SMAD4
c.1244-1247delAGAC	Hotspot mutation serious course of JPS with numerous cases of polyps, tumors located in the stomach and intestines	Howe et al[106]
BMPR1A
c.230+452_333+441dup 1995	Frameshift mutation producing a truncated protein (p.D112NfsX2)	Yamaguchi et al[107]

JPS: Juvenile polyposis syndrome.

Table 6 STK11 mutations associated with colorectal cancer caused by peutz-jeghers syndrome

STK11 mutation	Mutation type	Effect on protein	Ref.
c.511 G > A	Missense mutation	G171S	Dong et al[127]
c. 595 G > A	Missense mutation	E199K	Dong et al[127]
c.622 G > A	Missense mutation	D208N	Dong et al[127]
c.644 G > A	Missense mutation	G215D	Dong et al[127]
c.941 C > A	Missense mutation	P314H	Resta et al[128]
c.1062 C > G	Missense mutation	F354L	Dong et al[127]
c.1100 C > T	Missense mutation	T367M	Dong et al[127]
c.842delC	Frameshift mutation	truncates	Dong et al[127], Bartosova et al[129]
IVS2 + 1A > G	Intronic splice site mutation		Bartosova et al[129]
OR4C45 c.767-768insAG	Frameshift mutation	truncates	Wang et al[121]
ZAN c.5767insG	Frameshift mutation	truncates	Wang et al[121]