Table 5.

The presence of additional pathogenic alterations beyond RB1 inactivation correlates with specific clinicopathologic features in retinoblastoma

		RB1 inactivation only (n=15)	RB1 + additional pathogenic alteration# (n=13)	p-value
Age at diagnosis, median (range)		14 months (3–92)	27 months (2–19)	p=0.37
Germline RB1 alteration		8 (54%)	2 (15%)	p=0.05
Laterality	Unilateral	7 (47%)	11 (85%)	p=0.05
	Bilateral	8 (53%)	2 (15%)
IICR tumor group	Group D	4 (27%)	1 (8%)	p=0.33
	Group E	11 (73%)	12 (92%)
Clinical TNM	cT2	7 (47%)	8 (62%)	p=0.48
stage	cT3 or cT4	8 (53%)	5 (38%)
Extraocular extension on MRI		4 (27%)	4 (31%)	p=1.00
Pathologic TNM	pT1	14 (93%)	8 (62%)	p=0.07
stage	pT2 - pT4	1 (7%)	5 (38%)
Optic nerve involvement		3 (20%)	7 (58%)	p=0.06
Choroidal invasion		3 (20%)	4 (33%)	p=0.66
Histologic grade	Grade 1 or 2	10 (67%)	1 (8%)	P<0.01
	Grade 3 or 4	5 (33%)	12 (92%)
Anaplastic histology		7 (47%)	11 (85%)	p=0.05

^#Additional likely pathogenic alterations beyond RB1 inactivation that were present in these 13 tumors included: focal high-level MYCN amplification (2), MDM2 amplification (1), RAF1 amplification (1), truncating BCOR mutation (4), truncating MGA mutation (2), truncating ARID1A mutation (2), and ATRX missense mutation (1). Somatic variants of unknown significance (e.g. missense mutations not recurrently found in the COSMIC database and involving genes not known to be recurrently mutated in retinoblastoma) were not considered as likely pathogenic alterations beyond RB1 inactivation for this analysis.