Loss of fragile histidine triad and amplification of 1p36.22 and 11p15.5 in primary gastric adenocarcinomas

Table 1 Clinical characteristics, risk factors and overall genomic imbalances in 20 gastric adenocarcinomas

No.	ID	Sex/age (yr)	T/N/M stage	Tumor type	Histology grade (differentiated)	Tumor location	Smoke history	Drink history	Genomic size of total gain (Mb)	Genomic size of total loss (Mb)	Net imbalances (Mb) (%)2
1	T64	M/75	T3/N3/M0	Tubular	Poorly	Upper (CR), lower (AA)	Y	Y	290.7	147.3	+143.4 (4.8)
2	TW0800	M/65	T3/N3/M0	Tubular	Poorly	Upper (CR/GF), central (GB)	N	N	388.9	205.3	+183.6 (5.6)
3	T74	M/58	T3/N3/M0	Tubular	Poorly	Central (GB)	N	Y	290.1	412.3	-122.2 (4.1)
4	TW0784	M/75	T3/N1/M0	Tubular	Poorly	Upper (CR/GF)	N	N	3.4	0	+3.4 (0.1)
5	T66	M/50	T3/N2/M0	Tubular	Poorly	Lower (AA)	N	Y	34.2	0	+34.2 (1.1)
6	T78	F/59	T3/N1/M0	Tubular	Poorly	Lower (AA)	N	N	146.2	0	+107.4 (3.6)
7	T41	M/73	T3/N2/M0	Tubular	Poorly	Lower (AA/P)	Y	Y	7.2	0	+7.2 (0.2)
8	T47	F/52	T3/N1/M0	Tubular	Poorly	Lower (AA)	N	N	0.0	0.0	0.0 (0.0)
9	T38	F/53	T2/N1/M0	Tubular	Poorly	Lower (AA/P)	N	N	294.3	37.4	+256.9 (8.6)
10	TW0796	M/56	T3/N1/M0	Tubular	Poorly	Lower (AA/P)	Y	Y	224.4	11.9	+212.5 (7.1)
11	TW0807	M/54	T3/N0/M0	Tubular	Poorly	Lower (AA/P)	Y	Y	191.7	43.7	+148.0 (4.9)
12	TW0813	F/57	T3/N2/M0	Tubular1	Poorly	Lower (AA/P)	N	N	76.1	54.6	+21.5 (0.7)
13	T52	M/73	T3/N2/M0	Tubular	Moderately	Upper (CR/GF)	N	N	333.9	361.8	-27.9 (0.9)
14	TW0797	M/62	T3/N1/M0	Tubular	Moderately	Upper (CR/GF)	N	Y	161.1	0	+161.1 (5.4)
15	TW0782	M/53	T3/N2/M0	Tubular	Moderately	Upper (CR/GF)	Y	N	290.1	108.3	+181.8 (6.1)
16	TW0780	F/59	T2/N0/M0	Tubular	Moderately	Lower (AA/P)	N	N	4.1	4.16	-0.06 (0.0)
17	T75	M/69	T3/N2/M0	Tubular	Moderately	Lower (AA)	Y	Y	28	0	+28.0 (0.9)
18	T76	F/59	T3/N1/M0	Mucinous	Poorly	Upper (CR/GF)	Y	Y	99.1	0	+99.1 (3.3)
19	TW0789	M/64	T3/N1/M0	Mucinous	Poorly	Lower (AA/P)	N	N	504.5	167.6	+336.9 (11.2)
20	TW0774	F/76	T3/N3/M0	Mucinous	Poorly	Lower (AA/P)	N	N	41.4	90.4	-49.0 (1.6)

¹Signet ring cell;

²Percent of net imbalances calculated based on 3000 Mb of genome size. F: Female; M: Male; T: Tumor; N: Node; M: Metastasis ; CR: Cardiac region; GF: Gastric fundus; GB: Gastric body; AA: Antral area; P: Pylorus; Y: Yes; N: No.

Table 2 Amplification segments and the genes involved

Chr. region	Amp	Gain	SRO, bp (hg 18)	Size (kb)	Genes	Selected references
1p36.221	2	1	10 587 540-11 006 299	418.7	PEX14, CASZ1, C1orf127, TARDBP	N/A
1q21.2	1	3	148 737 723-149 062 575	324.9	TARS2, ECM1, ADAMTSL43, MCL13, ENSA2, GOLPH3L, HORMAD13, CTSS, CTSK, ARNT2	Gastric cancer[7], adenocarcinoma of the gastroesophageal junction[8]3, basal/luminal breast cancer[9]3, hepatocellular carcinoma[10]
8p23.1	2	3	10 475 239-10 562 632 10 681 251-10 943 920 11 250 228-11 887 602	87.4 262.7 637.4	RP1 L1PINX1, XKR6TDH, FAM167A, BLK, GATA4234, NEIL22, FDFT123, CTSB23	Gastric cancer[7,11], esophageal adenocarcinoma[12,13]3,[14],[15]3, adenocarcinomas of the gastroesophageal junction[16]3, small bowel adenocarcinoma[17]
8q24.21	1	11	128 331 422-128 837 626	506.2	POU5F1B, LOC727677, MYC23	Various cancer[5], esophageal adenocarcinoma[14], gastric cancer[18],[19]2,[20], papillary renal cell carcinoma[21]3
10q26.12	1	0	121 881 486-123 931 430	2050.0	PPAPDC1A, LOC283089, WDR11, FGFR23, ATE13, NSMCE4A3, TACC23	Breast cancer[22]3, gastric carcinoma[20]
10q26.13			126 212 750-126 362 686	149.9	LHPP, FAM53B
11p15.51	1	0	1 175 114-1 556 281	381.2	MUC5B, LOC255512, TOLLIP, BRSK2, HCCA2, DUSP8, LOC33865	N/A
11p13	2	1	34 675 094-35 068 916	393.8	APIP3, PDHX3	Breast cancer[23], gastric cancer cell line[24], head and neck squamous cell carcinoma cell line[25]3
11q13.2q13.3	3	0	68 912 663-69 256 388	343.7	CCND123, ORAOV123, FGF193	Various cancers[5], gastric cancer[7,11,20],[26]2, hepatocellular carcinoma[27]2, esophageal adenocarcinoma[14], esophageal and gastric cancer[26], esophageal squamous cell carcinoma[28]3, laryngeal/pharyngeal cancer[29]3
12p12.1	2	2	25 150 060-25 437 736	287.7	LRMP3, CASC1, LYRM5, KRAS23	Various cancers[5], esophageal adenocarcinoma[14], gastric cancer[11,20],[30]2, ovarian cancer[31]3
12q15	2	0	67 475 003-67 875 102 68 037 717-68 318 830	400.1 281.1	MDM22, CPMYEATS4 (GAS41)3, FRS23, CCT23, LRRC10	Various cancers[5], esophageal adenocarcinoma[14], gastric cancer[20,32], liposarcomas[33]3, melanoma cell line[34]3
17q12	2	1	35 000 176-35 150 077	149.9	NEUROD2, PPP1R1B2, STARD32, TCAP, PNMT2, PERLD12, ERBB22, C17orf37, GRB72	Various cancers[5], gastric cancer[11,20],[35-37]2,[38],[39]2
18q11.2	3	2	17 800 202-18 425 167	625.0	GATA634, CTAGE1	Pancreatic carcinoma[40,41]3, esophageal adenocarcinoma[14],[42]3
19q12	3	3	33 606 476-35 037 396	1340.9	LOC148145, LOC10050583, UQCRFS12, LOC284395, VSTM2B, POP42, PLEKHF12, C19orf122, CCNE12	Gastric cancer[43]2,[44],[45]2, esophageal/gastric cardiac adenocarcinoma[12]
20q13.2	1	6	51 568 862-51 993 797	424.9	ZNF2173, SUMO1P1, BCAS13	Esophageal adenocarcinoma[14], adenocarcinoma of the gastroesophageal junction[46]3, breast cancer[47], gastric adenocarcinoma[48], glioblastoma[49], various cancers[50]

¹Novel amplicon;

²Gene and references that are overexpressed when amplified in gastric cancer;

³Genes (and references) that are overexpressed when amplified in types of cancer other than gastric cancer;

⁴Underexpression has been reported in gastric cancer. SRO: Smallest region of overlap; N/A: Not available.

Table 3 Summary of losses of FHIT at 3p14.2 and of PDCH7 at 4p15.1

Gene	Chromosome region	Case	Genomic coordinates (NCBI build 36.3; hg18)	Size (kb)
FHIT (HD)	3p14.2	T38	60 775 135-61 162 550	387.4
FHIT	3p14.2	TW0789	59 762 657-60 525 130	762.5
FHIT intron	3p14.2	TW800	60 781 394-60 987 631	206.2
FHIT	3p14.2	TW813	59 900 085-60 543 794	437.5
FHIT etc.	3pter-p11.2	T74	37 570-88 331 466	88 300.0
FHIT intron	3p14.1	T782	60 343 805-60 493 871	150.1
PDCH7 etc.	4p16.3-p13	T64	2 431 351-44 331 469	41 900.0
PDCH7	4p15.1	TW789	29 575 024-30 487 701	912.7
PDCH7 etc.	4pter-p14	TW807	191-37 525 019	37 500.0
PDCH7 etc.	4pter-p14	TW774	191-38 356 422	38 400.0
PDCH7	4p15.1	TW782	30 393 830-30 637 746	243.9
PDCH7 etc.	4pter-p14	TW813	191-38 993 759	39 000.0

HD: Homozygous deletion.