Characterizing temporal genomic heterogeneity in pediatric low-grade gliomas

Lazow, Margot A.; Hoffman, Lindsey; Schafer, Austin; Osorio, Diana S.; Boué, Daniel R.; Rush, Sarah; Wright, Erin; Lane, Adam; DeWire-Schottmiller, Mariko D.; Smolarek, Teresa; Sipple, Jared; Taggert, Heather; Reuss, Jaime; Salloum, Ralph; Hummel, Trent R.; de Blank, Peter; Pillay-Smiley, Natasha; Sutton, Mary E.; Asher, Anthony; Stevenson, Charles B.; Drissi, Rachid; Finlay, Jonathan L.; Fouladi, Maryam; Fuller, Christine

doi:10.1186/s40478-020-01054-w

Acta Neuropathologica Communications

Table 2 Overview of temporal genomic heterogeneity

From: Characterizing temporal genomic heterogeneity in pediatric low-grade gliomas

	BRAF fusion	BRAF V600E	CDKN2A deletion	H3K27M mut.	IDH1 mut.	FGFR1 fusion	NTRK2 fusion	MYB fusion	MYBL1 fusion	ATRX loss
Entire Cohort (all diagnoses, n = 45)
Patients with paired tumor samples tested	34	44	26	21	28	28	17	16	12	18
Conserved
Remained positive (S, I)	17 (S = 9, I = 1)	2 (S = 0, I = 0)	4 (S = 1, I = 0)	0	2* (S = 0, I = 1)	0	0	0	0	1^# (S = 0, I = 1)
Remained negative (S, I)	17 (S = 4, I = 3)	41 (S = 17, I = 5)	11 (S = 4, I = 1)	21 (S = 9, I = 3)	26 (S = 10, I = 2)	27 (S = 10, I = 4)	17 (S = 5, I = 3)	16 (S = 5, I = 3)	12 (S = 4, I = 2)	17 (S = 7, I = 3)
Changed
Acquired (S, I)	0	0	7 (S = 3, I = 1)	0	0	1 (S = 0, I = 0)	0	0	0	0
Lost (S, I)	0	1 (S = 0, I = 0)	4^a (S = 1, I = 2)	0	0	0	0	0	0	0
By Histolopathologic diagnosis:
Pilocytic or Pilomyxoid Astroyctoma (n = 28)
Patients with paired tumor samples tested	23	28	19	13	15	19	9	10	7	10
Conserved
Remained positive (S, I)	15 (S = 9, I = 1)	0	4 (S = 2, I = 0)	0	0	0	0	0	0	0
Remained negative (S, I)	8 (S = 2, I = 1)	27 (S = 14, I = 2)	6 (S = 2, I = 0)	13 (S = 6, I = 1)	15 (S = 7, I = 1)	18 (S = 8, I = 2)	9 (S = 3, I = 1)	10 (S = 3, I = 1)	7 (S = 2, I = 1)	10 (S = 5, I = 1)
Changed
Acquired (S, I)	0	0	6 (S = 2, I = 1)	0	0	1 (S = 0, I = 0)	0	0	0	0
Lost (S, I)	0	1 (S = 0, I = 0)	3^a (S = 1, I = 1)	0	0	0	0	0	0	0
Diffuse Astrocytoma (n = 7)
Patients with paired tumor samples tested	3	6	2	5	7	5	4	2	1	2
Conserved
Remained positive (S, I)	0	0	0	0	2* (S = 0, I = 1)	0	0	0	0	1^# (S = 0, I = 0
Remained negative (S, I)	3 (S = 0, I = 1)	6 (S = 1, I = 1)	0 (S = 0, I = 0)	5 (S = 1, I = 0)	5 (S = 1, I = 0)	5 (S = 1, I = 1)	4 (S = 0, I = 1)	2 (S = 0, I = 1)	1 (S = 0, I = 0)	1 (S = 0, I = 1)
Changed
Acquired (S, I)	0	0	0	0	0	0	0	0	0	0
Lost (S, I)	0	0	1 (S = 0, I = 1)	0	0	0	0	0	0	0
Ganglioglioma (n = 5)
Patients with paired tumor samples tested	4	5	1	0	2	1	1	1	1	2
Conserved
Remained positive (S, I)	2 (S = 1, I = 0)	2 (S = 0, I = 0)	0	0	0	0	0	0	0	0
Remained negative (S, I)	2 (S = 0, I = 0)	3 (S = 1, I = 0)	1 (S = 0, I = 0)	0	2 (S = 0, I = 0)	1 (S = 0, I = 0)	1 (S = 0, I = 0)	1 (S = 0, I = 0)	1 (S = 0, I = 0)	2 (S = 0, I = 0)
Changed
Acquired (S, I)	0	0	0	0	0	0	0	0	0	0
Lost (S, I)	0	0	0	0	0	0	0	0	0	0
Other LGGs (n = 5)
Patients with paired tumor samples tested	4	5	4	3	4	3	3	3	3	4
Conserved
Remained positive (S, I)	0	0	0	0	0	0	0	0	0	0
Remained negative (S, I)	4 (S = 2, I = 1)	5 (S = 2, I = 1)	3 (S = 2, I = 0)	3 (S = 2, I = 1)	4 (S = 2, I = 1)	3 (S = 2, I = 1)	3 (S = 2, I = 1)	3 (S = 2, I = 1)	3 (S = 2, I = 1)	4 (S = 2, I = 1)
Changed
Acquired (S, I)	0	0	1 (S = 2, I = 1)	0	0	0	0	0	0	0
Lost (S, I)	0	0	0	0	0	0	0	0	0	0

Results for the entire cohort (all histologic diagnoses) are shown together at the top, followed by results for each histologic diagnosis subgroup individually. The number of patients who had testing for a given genetic alteration performed on paired tumor specimens is shown in the top row of each category. Subsequent rows illustrate the number of patients with conversed or changed (acquired or lost) status for given genetic alterations, specifying the number of patients who received systemic therapy (“S”) or irradiation (“I”) between surgeries
* One of these patients had conserved IDH1 R132H mutations (Patient #33) and the other had conserved IDH1 R132G mutations (Patient #32)
^#Although this patient had conserved ATRX loss demonstrated on IHC, sequencing revealed different ATRX mutations in the diagnostic and recurrent tumor samples, as described in the text
^aOne of these patients had CDKN2A testing performed on three tumor specimens, with CDKN2A deletions identified (conserved) on the first two tumor samples, and subsequently lost on the third (post-mortem) tumor sample

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