Identification of a neuronal transcription factor network involved in medulloblastoma development

Table 1 Common Insertion Sites (CISs) in Medulloblastomas and Cerebellum Controls

Gene	Chr	CIS width	N	I	GKC p-value	Other genes	Inferred MOA	CGC	MB- Mut	MB- CIS
A. Medulloblastomas
*Nfia*	4	28.6	20	27	<1E-14	-	Loss	-	-	Ptch
*Atxn2*	5	25	6	6	<1E-14	-	?	-	-	-
*Tead1*	7	19.1	6	7	3.9E-14	-	Gain	-	-	Ptch
*Tgif2*	2	0.8	3	4	0.0006	-	Gain	-	-	-
*Crebbp*	16	37.1	5	5	0.0009	-	Loss	S	Y	Ptch
*Dscr3*	16	18.3	5	6	0.0009	-	Loss	-	-	-
CIS13:72336914	13	44.3	5	6	0.0042	n/a	n/a	n/a	n/a	n/a
Pten*	19	50.2	4	5	0.0046	-	Loss	S/G	Y	Both
*Itgbl1*	14	43.4	5	5	0.0062	Fgf14	?	-	-	-
*Nfib*	4	24.7	7	9	0.0071	-	Gain	S	-	Ptch
Myt1l	12	67.2	8	10	0.0089	Pxdn,Tpo,Sntg2	Loss	-	-	-
Ankrd5	2	1071.3	8	15	0.0092	Plcb4, Pak7,Snap25	?	-	-	-
Slit3	11	494.3	8	12	0.012	-	Loss	-	-	-
*Tmem45b*	9	58.4	4	5	0.019	-	?	-	-	-
*Sfi1*	11	51	5	6	0.021	-	Loss	-	-	Both
CIS15:70979306	15	20.3	4	4	0.028	n/a	n/a	n/a	n/a	n/a
Fgf13	X	23.5	3	4	0.026	-	Gain	-	-	-
CIS3:147532546	3	140.5	4	7	0.043	n/a	n/a	n/a	n/a	n/a
L3mbtl4	17	221.6	7	7	0.043	Tmem200c	Loss	-	-	-
Adcy5	16	127.1	4	6	0.044	Ptblb	Loss	-	-	-
B. Cerebellum controls
*Faf1*	4	41.7	4	4	0.01	-	?
*l7Rn6*	7	10	3	3	0.018	Ccdc81	?
CIS6:31346217_240k	6	844	6	8	0.045	n/a	n/a
Ric3	7	99	4	4	0.035	Tub	?
CIS9:68415409_240k	9	1738	9	11	0.016	n/a	n/a

Genes associated with CISs, the chromosomes to which they map, and the genomic extent of each CIS are shown. GKC p-values are from the Genome Kernel Convolution analysis (see Methods). The number of tumours (N) and T2Onc insertions (I) which define each GKC CIS, together with other genes within the CIS interval, are also shown. The position and orientation of SB insertions can be used to infer the mode of action (MOA) of insertion (e.g. [28]). Most of the CISs have insertions distributed throughout the genes they identify, and in both orientations, suggesting loss of function (Loss). Both of the CIS genes which have proven tumour suppressor activity (Pten and Crebbp) show this pattern. An excess of inserts in the 5’ end of a gene, and in a +ve orientation with respect to transcription, implies upregulation of expression (Gain) through SB enhancer function [34]. CGC – Genes known to cause cancer due to somatic (S) or germline (G) mutations from the Cancer Genome Census (http://www.sanger.ac.uk/genetics/CGP/Census/). MB-Mut – Somatic mutations previously identified in MB [11, 12, 14, 15]. MB-CIS – previously identified as an MB CIS [30] in either the Ptch model (Ptch) or the Ptch and p53 model (both). *Pten, was also identified as a CIS within haematological tumours (data not shown) but is included here as it is a known MB gene. For details, see Methods.

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