Table 2.
Overview of temporal genomic heterogeneity
| 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) |
4a (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) |
3a (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