DNA Copy Number Gains at Loci of Growth Factors and Their Receptors in Salivary Gland Adenoid Cystic Carcinoma

DOI: 10.1158/1078-0432.CCR-06-2555 Published June 2007

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Fig. 1.
Frequency plots of gains and losses for chromosomes 1 to 22 as determined by array CGH. Percentages of gains (positive axis) and losses (negative axis) are shown for each BAC clone in all ACCs analyzed.
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Fig. 2.
Kaplan-Meier plot for overall survival in primary ACCs. Patients with 17 or more chromosomal events in their tumors show a significantly poorer survival (P = 0.02) than patients with less chromosomal aberrations.

Table 1.

Amplifications in ACC

NOTE: Overview of the amplifications was detected in 18 primary ACCs. The amplicon sizes in mega-bps (Mbps) and the candidate oncogenes that are found in the region are also depicted.

Table 2.

Most frequent aberrations in ACC

Cytoband			Size of region (Mbps)	No. tumors, n (%)	Candidate genes
Gains	1p36.33-p35.3	27.70	8 (44)	E2F2, TNFRSF4
		1p35.2-p33	16.11	8 (44)	CSF3R, PTPRF, HDAC1
		2q37.3	0.58	5 (28)	—
		4p16.3	1.69	5 (28)	FGFR3, CTBP1
		5q32-q33.1	3.67	7 (39)	PDGFRB
		8q24.3	3.80	7 (39)	PLEC1
		9q33.3-q34.3	11.44	13 (72)	ABL1, NOTCH1, TRAF2
		11p15.5	1.82	6 (33)	MUC2, HRAS
		11q13.3	0.37	11 (61)	FGF3, FGF4, FGF19
		11q23.3	2.30	11 (61)	IL10RA, MLL, CBL
		12q13.2-q14.1	1.77	5 (28)	ERBB3, STAT6, RAB5B, WNT1
		13q34	1.04	6 (33)	TFDP1, GAS6
		16p13.3	4.42	8 (44)	MMP25, SOX8, RAB26
		16q24.3	0.05	7 (39)	—
		17p13.3	1.84	7 (39)	CRK
		17q11.2-q25.3	55.15	5 (28)	ERBB2, PPMD1, ITGB4
		19p13.3-p13.11	17.90	14 (78)	RAB8A, FGF22, ICAM5
		19q12-q13.43	26.75	14 (78)	TGFB1, BCL3
		20q13.33	2.64	5 (28)	SOX18, PTK6, RTEL1, TNFRSF6B
		21q22.3	3.21	11 (61)	ITGB2, PTTG1IP, COL18A1, S100B
		22q13.33	1.21	13 (72)	ECGF1, MAPK12
Losses	1p21.3-p12	23.73	2 (11)	ST7L
		5q21.1	2.49	3 (17)	ST8SIA4
		5q21.3-q23.2	18.82	3 (17)	APC
		9p22.3-p13.3	20.47	3 (17)	CDKN2A
		12q12-q14.1	23.01	2 (11)	KRT7, HOXC5
		13q14.3-q21.32	13.22	2 (11)	PCDH17, PCDH9, INTS6
		14q11.2-q31.3	64.52	4 (22)	SEL1, DLG7, NFKBIA
		17p13.1-q11.1	12.93	2 (11)	LLGL1
		20q11.23-q12	1.98	3 (17)	DHX35

NOTE: Most frequently gained (>25%) and lost (>10%) minimal common regions of overlap were detected by array CGH in 18 primary ACCs, together with candidate oncogenes and tumor suppressor genes. The size of the aberration is depicted in mega-bps (Mbps).

Table 3.

Significantly different alterations between tumors with and without metastasis/recurrence

Cytoband	Size (Mbps)	Bp position start	Bp position end	No. clones	P	FDR value
4p16.3	1.09	1764749	2859130	3	0.03	0.15
11q23.3-q24.1	0.62	120648888	121267168	6	0.05	0.20
16p13.3	0.78	3299612	4084406	3	0.05	0.20
16q24.1-q24.2	3.73	83444369	87172104	4	0.03	0.15
17p13.1	0.89	6894326	7781828	6	0.03	0.15

NOTE: Chromosomal regions were analyzed by array CGH with significantly different alterations between tumors with metastasis/recurrence during follow-up and those without. Sizes of the regions are depicted in mega-bps (Mbps), together with start and end sequences of the BAC clones in bp. Regions consisting of less than three clones were not considered reliable.
Abbreviation: FDR, false discovery rate.