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Long survival in a child with a mutated K27M-H3.3 pilocytic astrocytoma.

Hochart A, Escande F, Rocourt N, Grill J, Koubi-Pick V, Beaujot J, Meignan S, Vinchon M, Maurage CA, Leblond P - Ann Clin Transl Neurol (2015)

Bottom Line: We report the first case of a child with a H3F3A K27M mutated pilocytic astrocytoma, who presented with a 10 years survival, and underwent spontaneous malignant transformation.H3F3A K27M mutations are rarely observed in benign neoplasms and may be associated with an adverse outcome.This mutation might not be the major driver that led to the onset of tumorigenesis, and we could consider that the associated TP53 mutation, would be required for malignant transformation.

View Article: PubMed Central - PubMed

Affiliation: Pediatric Oncology Unit, Oscar Lambret Center Lille, France.

ABSTRACT
We report the first case of a child with a H3F3A K27M mutated pilocytic astrocytoma, who presented with a 10 years survival, and underwent spontaneous malignant transformation. The complex tumoral chromosomal rearrangements were consistent for genomic instability and for the histopathological features of malignant transformation into glioblastoma. H3F3A K27M mutations are rarely observed in benign neoplasms and may be associated with an adverse outcome. This mutation might not be the major driver that led to the onset of tumorigenesis, and we could consider that the associated TP53 mutation, would be required for malignant transformation.

No MeSH data available.


Related in: MedlinePlus

aCGH and H3F3A K27 mutational status in the first tumor sample resected in 2002 (left column) and the recurrence sample (right column). (A and C) Array comparative genomic hybridization (aCGH) genome plots indicating no aberration in the tumor of 2002 compared to the complex profile in 2012, which demonstrated multiple chromosome rearrangements with losses in large chromosomal regions in 5q, 8, 9q, 10, 12q, 13q, 14, 16q, 17, 18q, and 21 and gain of 9p. Focal high copy number amplification was observed in segments, including PDGFR, EGFR and MDM2/CDK4 genes. (B and D) Representative pyrograms showing the K27M (wt AAG→ ATG) mutation in tumor recurrence and in the primary tumor leading to an amino acid exchange from lysine (Lys) 27 to methionine (Met).
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fig03: aCGH and H3F3A K27 mutational status in the first tumor sample resected in 2002 (left column) and the recurrence sample (right column). (A and C) Array comparative genomic hybridization (aCGH) genome plots indicating no aberration in the tumor of 2002 compared to the complex profile in 2012, which demonstrated multiple chromosome rearrangements with losses in large chromosomal regions in 5q, 8, 9q, 10, 12q, 13q, 14, 16q, 17, 18q, and 21 and gain of 9p. Focal high copy number amplification was observed in segments, including PDGFR, EGFR and MDM2/CDK4 genes. (B and D) Representative pyrograms showing the K27M (wt AAG→ ATG) mutation in tumor recurrence and in the primary tumor leading to an amino acid exchange from lysine (Lys) 27 to methionine (Met).

Mentions: After genomic DNA extraction, a mutation analysis of hotspot codons 27 and 34 of the H3F3A gene was investigated using pyrosequencing (Qiagen, Valencia, CA, USA). Exon 4 of the IDH1/2 genes, exon 15 of the BRAF gene and all of the exons of the activin A receptor type I (ACVR1) and TP53 genes were also analyzed using Sanger sequencing (Applied Biosystems, Foster City, CA, USA). Unexpectedly, these results showed the exclusive presence of a K27M (c.83A>T, p.Lys27Met) H3.3 mutation in the primary tumor from 2002. In the tumor recurrence from 2012, K27M mutation associated with a TP53 mutation (c.817C>T, p.Arg273Cys) were detected (Fig.3). No IDH1/2, PTEN, BRAF, and ACVR1 mutations were found in both tumors.


Long survival in a child with a mutated K27M-H3.3 pilocytic astrocytoma.

Hochart A, Escande F, Rocourt N, Grill J, Koubi-Pick V, Beaujot J, Meignan S, Vinchon M, Maurage CA, Leblond P - Ann Clin Transl Neurol (2015)

aCGH and H3F3A K27 mutational status in the first tumor sample resected in 2002 (left column) and the recurrence sample (right column). (A and C) Array comparative genomic hybridization (aCGH) genome plots indicating no aberration in the tumor of 2002 compared to the complex profile in 2012, which demonstrated multiple chromosome rearrangements with losses in large chromosomal regions in 5q, 8, 9q, 10, 12q, 13q, 14, 16q, 17, 18q, and 21 and gain of 9p. Focal high copy number amplification was observed in segments, including PDGFR, EGFR and MDM2/CDK4 genes. (B and D) Representative pyrograms showing the K27M (wt AAG→ ATG) mutation in tumor recurrence and in the primary tumor leading to an amino acid exchange from lysine (Lys) 27 to methionine (Met).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4402089&req=5

fig03: aCGH and H3F3A K27 mutational status in the first tumor sample resected in 2002 (left column) and the recurrence sample (right column). (A and C) Array comparative genomic hybridization (aCGH) genome plots indicating no aberration in the tumor of 2002 compared to the complex profile in 2012, which demonstrated multiple chromosome rearrangements with losses in large chromosomal regions in 5q, 8, 9q, 10, 12q, 13q, 14, 16q, 17, 18q, and 21 and gain of 9p. Focal high copy number amplification was observed in segments, including PDGFR, EGFR and MDM2/CDK4 genes. (B and D) Representative pyrograms showing the K27M (wt AAG→ ATG) mutation in tumor recurrence and in the primary tumor leading to an amino acid exchange from lysine (Lys) 27 to methionine (Met).
Mentions: After genomic DNA extraction, a mutation analysis of hotspot codons 27 and 34 of the H3F3A gene was investigated using pyrosequencing (Qiagen, Valencia, CA, USA). Exon 4 of the IDH1/2 genes, exon 15 of the BRAF gene and all of the exons of the activin A receptor type I (ACVR1) and TP53 genes were also analyzed using Sanger sequencing (Applied Biosystems, Foster City, CA, USA). Unexpectedly, these results showed the exclusive presence of a K27M (c.83A>T, p.Lys27Met) H3.3 mutation in the primary tumor from 2002. In the tumor recurrence from 2012, K27M mutation associated with a TP53 mutation (c.817C>T, p.Arg273Cys) were detected (Fig.3). No IDH1/2, PTEN, BRAF, and ACVR1 mutations were found in both tumors.

Bottom Line: We report the first case of a child with a H3F3A K27M mutated pilocytic astrocytoma, who presented with a 10 years survival, and underwent spontaneous malignant transformation.H3F3A K27M mutations are rarely observed in benign neoplasms and may be associated with an adverse outcome.This mutation might not be the major driver that led to the onset of tumorigenesis, and we could consider that the associated TP53 mutation, would be required for malignant transformation.

View Article: PubMed Central - PubMed

Affiliation: Pediatric Oncology Unit, Oscar Lambret Center Lille, France.

ABSTRACT
We report the first case of a child with a H3F3A K27M mutated pilocytic astrocytoma, who presented with a 10 years survival, and underwent spontaneous malignant transformation. The complex tumoral chromosomal rearrangements were consistent for genomic instability and for the histopathological features of malignant transformation into glioblastoma. H3F3A K27M mutations are rarely observed in benign neoplasms and may be associated with an adverse outcome. This mutation might not be the major driver that led to the onset of tumorigenesis, and we could consider that the associated TP53 mutation, would be required for malignant transformation.

No MeSH data available.


Related in: MedlinePlus