Details

Autor(en) / Beteiligte

• Zhong, Yiming
• Schubert, Jeffrey
• Wu, Jinhua
• Xu, Feng
• Lin, Fumin
• Cao, Kajia
• Zelley, Kristin
• Luo, Minjie
• Foster, Jessica B.
• Cole, Kristina A.
• MacFarland, Suzanne P.
• Resnick, Adam C.
• Storm, Phillip B.
• Li, Marilyn M.

Titel

A germline PALB2 pathogenic variant identified in a pediatric high-grade glioma

Ist Teil von

• Cold Spring Harbor molecular case studies, 2020-08, Vol.6 (4), p.a005397

Ort / Verlag

Cold Spring Harbor: Cold Spring Harbor Laboratory Press

Erscheinungsjahr

2020

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• PALB2 (partner and localizer of BRCA2) gene encodes a protein that colocalizes with BRCA2 in nuclear foci and likely permits the stable intranuclear localization and accumulation of BRCA2 . PALB2 plays a critical role in maintaining genome integrity through its role in the Fanconi anemia and homologous recombination DNA repair pathways. It has a known loss-of-function disease mechanism. Biallelic PALB2 pathogenic variants have been described in autosomal recessive Fanconi anemia. Heterozygous pathogenic variants in PALB2 are associated with increased risk for female and male breast cancer and pancreatic cancer ( Science 324: 217; Cancer Res 71: 2222–2229; N Engl J Med 371: 497–506). Heterozygous germline PALB2 mutations have also been observed in patients with medulloblastoma ( Lancet Oncol 19: 785–798). However, PALB2 -related cancer predisposition to high-grade gliomas has not been reported. Here we report a germline PALB2 pathogenic variant (c.509_510delGA, p.Arg170Ilefs*14, NM_024675.3) found in a pediatric patient with high-grade glioma. This variant was first identified by tumor sequencing using the Children's Hospital of Philadelphia (CHOP) Comprehensive Solid Tumor Panel and then confirmed to be a germline change using the CHOP Comprehensive Hereditary Cancer Panel on DNA from a blood sample of this patient. Parental studies showed that this variant was paternally inherited. Further studies are needed to illustrate if pathogenic variants in PALB2 convey increased risk to developing brain tumor. This case also highlights the potential of identifying germline mutation through tumor sequencing.