Introduction
Materials and methods
Tumor samples and controls
Tumor | Pathology | Grade | Location | Sex | Age | BRAF status |
---|---|---|---|---|---|---|
a. | ||||||
PGNT | Papillary glioneuronal | I | Frontal lobe | M | 14 | nd |
PA1 | Pilocytic astrocytoma | I | Posterior fossa | F | 16 |
KIAA1549-BRAF exon 16-exon 9 |
PA2 | Pilocytic astrocytoma | I | Posterior fossa | M | 12 |
KIAA1549-BRAF exon 16-exon 9 |
PA3 | Pilocytic astrocytoma | I | Posterior fossa | M | 14 |
KIAA1549-BRAF exon 16-exon 9 |
PA5 | Pilocytic astrocytoma | I | Posterior fossa | F | 3 |
KIAA1549-BRAF exon 16-exon 9 |
PA6 | Pilocytic astrocytoma | I | Cerebellum | F | 8 |
KIAA1549-BRAF exon 15-exon 9 |
PA7 | Pilocytic astrocytoma | I | Cerebellum | M | 1 |
KIAA1549-BRAF exon 16-exon 11 |
PA8 | Pilocytic astrocytoma | I | Cerebellum | M | 1 |
KIAA1549-BRAF exon 16-exon 9 |
PA9 | Pilocytic astrocytoma | I | Cerebellum | F | 2 |
KIAA1549-BRAF exon 16-exon 11 |
PA10 | Pilocytic astrocytoma | I | Cerebellum | M | 2 |
KIAA1549-BRAF exon 16-exon 9 |
PA11 | Pilocytic astrocytoma | I | Cerebellum | M | 6 |
KIAA1549-BRAF exon 16-exon 9 |
PA12 | Pilocytic astrocytoma | I | Cerebellum | F | 11 |
KIAA1549-BRAF exon 15-exon 9 |
PA13 | Pilocytic astrocytoma | I | Posterior fossa | M | 4 |
KIAA1549-BRAF exon 16-exon 9 |
PA14 | Pilocytic astrocytoma | I | Posterior fossa | F | 6 |
KIAA1549-BRAF exon 16-exon 9 |
PA15 | Pilocytic astrocytoma | I | Posterior fossa | M | 9 |
KIAA1549-BRAF exon 16-exon 9 |
DA1 | Diffuse astrocytoma | II | Temporal lobe | F | 12 | No BRAFV600E
|
DA2 | Diffuse astrocytoma | II | Unknown | F | 14 | No BRAFV600E
|
DA3 | Diffuse astrocytoma | II | Occipital lobe | M | 4 | nd |
DA4 * | Diffuse astrocytoma | II | Unknown | M | 17 |
BRAFV600E present |
AA1 | Anaplastic astrocytoma | III | Conus medullaris | M | 15 | nd |
AA2 | Anaplastic astrocytoma | III | Temporal lobe | F | 3 | No BRAFV600E
|
AA3 * | Anaplastic astrocytoma | III | Unknown | F | 11 | No BRAFV600E
|
GBM1 | Glioblastoma | IV | Frontal lobe | F | 15 | No BRAFV600E
|
GBM2 | Glioblastoma | IV | Temporoparietal | M | 10 | No BRAFV600E
|
GBM3 | Glioblastoma | IV | Brainstem | F | 4 | nd |
GBM4 | Glioblastoma | IV | Left frontal lobe | F | 10 | No BRAFV600E
|
GBM5 | Glioblastoma | IV | Spinal cord | F | 7 | nd |
E1 | Ependymoma | III | Posterior fossa | M | 4 | |
E2 | Ependymoma | III | Parietal lobe | F | 6 | |
E3 | Ependymoma | II | Posterior fossa | F | 2 | |
E4 | Ependymoma | III | Posterior fossa | F | 2 | |
E5 | Ependymoma | II | Temporal lobe | M | 12 | |
E6 | Ependymoma | III | Posterior fossa | M | 6 | |
E7 | Ependymoma | III | Posterior fossa | M | 2 | |
E8 | Ependymoma | II | Supratentorial (frontal) | M | 14 | |
E9 | Ependymoma | II | Posterior fossa | M | 3 | |
E10 | Ependymoma | II | Posterior fossa | M | 4 | |
E11 | Ependymoma | III | Posterior fossa | F | nd | |
E12 | Ependymoma | III | Fourth ventricle | M | 1 | |
E13 | Ependymoma | II | Spinal seed | F | 6 | |
E14 | Ependymoma | III | Posterior fossa | F | 6 | |
M1 | Medulloblastoma | IV | Posterior fossa | M | 4 | |
M2 | Medulloblastoma | IV | Posterior fossa | M | 1 | |
M3 | Medulloblastoma | IV | Posterior fossa | F | 6 months | |
M4 | Medulloblastoma | IV | Posterior fossa | M | 7 | |
M5 | Medulloblastoma | IV | Posterior fossa | M | 3 | |
M6 | Medulloblastoma | IV | Posterior fossa | M | 9 | |
M7 | Medulloblastoma | IV | Posterior fossa | M | 7 | |
M8 | Medulloblastoma | IV | Posterior fossa | M | 9 | |
M9 | Medulloblastoma | IV | Posterior fossa | M | 4 | |
M10 * | Medulloblastoma | IV | Posterior fossa | F | 5 | |
R1 | Atypical Rhabdoid | IV | Brainstem | M | 1 | |
R2 | Atypical Rhabdoid | IV | Posterior fossa | F | 7 months | |
R3 | Atypical Rhabdoid | IV | Supratentorial | F | 2 | |
R4 | Atypical Rhabdoid | IV | Posterior fossa | M | 9 months | |
R5 | Atypical Rhabdoid | IV | Posterior fossa | F | 2 months | |
P1 | Choroid Plexus Papilloma | I | Intraventricular (frontal lateral ventricle) | M | 10 months | |
P2 | Choroid Plexus Papilloma | I | Posterior fossa | M | 1 | |
P3 | Choroid Plexus Papilloma | I | Left lateral ventricle | M | 3 | |
P4 | Choroid Plexus Papilloma | I | Unknown | F | nd | |
AC1 | Adult control cerebellum | Cerebellum | M | 22 | ||
AC2 | Adult control frontal lobe | Frontal lobe | M | 41 | ||
AC3 | Adult control cerebellum | Cerebellum | M | 21 | ||
AC4 | Adult control cerebellum | Cerebellum | M | 26 | ||
AC5 | Adult control frontal lobe | Frontal lobe | M | 82 | ||
AC6 | Adult control frontal lobe | Frontal lobe | M | 25 | ||
AC7 | Adult control frontal lobe | Frontal lobe | M | 27 | ||
b. | ||||||
PA16 | Pilocytic astrocytoma | I | Posterior fossa | M | 9 | nd |
PA17 | Pilocytic astrocytoma | I | Posterior fossa | M | 12 | nd |
PA18 | Pilocytic astrocytoma | I | Suprasellar | M | 3 |
KIAA1549-BRAF exon 15-exon 9 |
PA19 | Pilocytic astrocytoma | I | 3rd ventricle | M | 16 | nd |
PA20 | Pilocytic astrocytoma | I | Brain stem | F | 3 |
KIAA1549-BRAF exon 15-exon 9 |
PA21 | Pilocytic astrocytoma | I | Posterior fossa | F | 4 |
KIAA1549-BRAF exon 16-exon 9 |
PA22 | Pilocytic astrocytoma | I | Posterior fossa | M | 16 |
KIAA1549-BRAF exon 16-exon 9 |
PA23 | Pilocytic astrocytoma | I | Posterior fossa | F | 2 |
KIAA1549-BRAF exon 16-exon 11 |
PA24 | Pilocytic astrocytoma | I | Posterior fossa | F | 12 |
KIAA1549-BRAF exon 16-exon 9 |
GBM6 | Glioblastoma | IV | Midbrain/Thalamus | F | 14 | - |
GBM7 | Glioblastoma | IV | Occipital lobe | M | 4 months | - |
GBM8 | Glioblastoma | IV | Thalamic/intraventriclar | F | 10 | - |
GBM9 | Glioblastoma | II | Thalamic | M | 15 | - |
MicroRNA and gene expression arrays
Statistical analysis
Pathway analysis
Taqman microRNA assays
RT-qPCR
Results
Characterization of the pediatric brain tumor cohort
Pathology |
n
| Regulation | Total | |
---|---|---|---|---|
Up | Down | |||
Pilocytic astrocytoma | 14 | 42 | 49 | 91 |
Pilocytic astrocytomaa
| 14 | 27 | 33 | 60 |
Diffuse astrocytoma | 3 | 1 | 2 | 3 |
Anaplastic astrocytoma | 2 | 6 | 8 | 14 |
Glioblastoma | 5 | 0 | 5 | 5 |
Ependymoma | 14 | 60 | 75 | 135 |
Medulloblastoma | 9 | 25 | 35 | 60 |
Medulloblastomaa
| 9 | 10 | 29 | 39 |
Atypical Teratoid/Rhabdoid tumor | 5 | 15 | 17 | 32 |
Choroid plexus papilloma | 4 | 47 | 63 | 110 |
MicroRNA profile and the predicted targeted pathways in Pilocytic Astrocytomas
TargetID | p (Corr) | FC | Log FC |
---|---|---|---|
a. | |||
hsa-miR-224 | 0.00632 | 10.09 | 3.33 |
hsa-miR-542-5p | 0.00558 | 9.69 | 3.28 |
hsa-miR-542-3p | 0.02366 | 7.51 | 2.91 |
hsa-miR-450b-5p | 0.00285 | 6.89 | 2.78 |
hsa-miR-503 | 0.00120 | 6.80 | 2.76 |
hsa-miR-450a | 0.01211 | 6.67 | 2.74 |
hsa-miR-886-5p | 0.00551 | 6.17 | 2.62 |
hsa-miR-767-5p | 0.00002 | 4.94 | 2.31 |
HS_29 | 0.01811 | 4.41 | 2.14 |
hsa-miR-708 | 0.02645 | 3.92 | 1.97 |
hsa-miR-146a | 0.01076 | 3.84 | 1.94 |
hsa-miR-34a | 0.00268 | 3.13 | 1.65 |
solexa-539-2056 | 0.04379 | 3.03 | 1.60 |
hsa-miR-335* | 0.00486 | 2.81 | 1.49 |
hsa-miR-18b | 0.04529 | 2.79 | 1.48 |
hsa-miR-452* | 0.00000 | 2.58 | 1.37 |
hsa-miR-18a | 0.00441 | 2.56 | 1.36 |
hsa-miR-199a*:9.1 | 0.03622 | 2.56 | 1.36 |
hsa-miR-574-5p | 0.00000 | 2.39 | 1.26 |
hsa-miR-296-3p | 0.02907 | 2.36 | 1.24 |
hsa-miR-155 | 0.01372 | 2.33 | 1.22 |
hsa-miR-24-2* | 0.00000 | 2.33 | 1.22 |
hsa-miR-106a | 0.00149 | 2.32 | 1.21 |
hsa-miR-21* | 0.00073 | 2.22 | 1.15 |
HS_262.1 | 0.01814 | 2.16 | 1.11 |
hsa-miR-363 | 0.01021 | 2.07 | 1.05 |
hsa-miR-371-3p | 0.00002 | 2.03 | 1.02 |
b. | |||
hsa-miR-129-3p | 0.00062 | −44.25 | −5.47 |
hsa-miR-129* | 0.00000 | −27.08 | −4.76 |
hsa-miR-1224-5p | 0.00515 | −16.54 | −4.05 |
hsa-miR-124a:9.1 | 0.00357 | −15.84 | −3.99 |
hsa-miR-326 | 0.01508 | −12.16 | −3.60 |
hsa-miR-124 | 0.00073 | −9.66 | −3.27 |
hsa-miR-204 | 0.00140 | −9.65 | −3.27 |
hsa-miR-1296 | 0.00000 | −6.94 | −2.80 |
hsa-miR-885-5p | 0.00006 | −6.76 | −2.76 |
hsa-miR-128a:9.1 | 0.00149 | −5.78 | −2.53 |
hsa-miR-218 | 0.00504 | −5.72 | −2.52 |
hsa-miR-133b | 0.00000 | −5.57 | −2.48 |
hsa-miR-874 | 0.00013 | −5.52 | −2.46 |
hsa-miR-769-3p | 0.02429 | −4.96 | −2.31 |
hsa-miR-485-3p | 0.01589 | −4.70 | −2.23 |
hsa-miR-128b:9.1 | 0.00049 | −4.68 | −2.23 |
HS_182.1 | 0.00140 | −4.45 | −2.15 |
hsa-miR-107 | 0.00002 | −4.38 | −2.13 |
hsa-miR-383 | 0.00175 | −4.36 | −2.12 |
hsa-miR-656 | 0.00825 | −4.35 | −2.12 |
hsa-miR-124* | 0.03622 | −4.14 | −2.05 |
hsa-miR-584 | 0.00130 | −3.61 | −1.85 |
hsa-miR-7 | 0.00108 | −3.40 | −1.77 |
hsa-miR-548k | 0.01014 | −3.39 | −1.76 |
hsa-miR-1237 | 0.00149 | −3.21 | −1.68 |
hsa-miR-299-5p | 0.01076 | −3.20 | −1.68 |
hsa-miR-1179 | 0.01508 | −2.92 | −1.55 |
hsa-miR-487b | 0.03622 | −2.75 | −1.46 |
HS_231 | 0.00367 | −2.73 | −1.45 |
hsa-miR-329 | 0.00101 | −2.47 | −1.30 |
hsa-miR-154* | 0.00566 | −2.47 | −1.30 |
hsa-miR-889 | 0.01811 | −2.15 | −1.11 |
hsa-miR-135a | 0.02645 | −2.06 | −1.04 |