Molecular features of pleomorphic xanthoastrocytoma

Han Zou; Yumei Duan; Dongliang Wei; Yiqian Zhang; Jiacheng Dai; Junzhi Li; Xiaojie Li; Jianhua Zhou; Zhixiong Liu; Zhongyuan Jin; Zhou Zhang; Yang Yu; Zhongliang Hu

doi:10.1016/j.humpath.2018.08.038

Molecular features of pleomorphic xanthoastrocytoma

Hum Pathol. 2019 Apr:86:38-48. doi: 10.1016/j.humpath.2018.08.038. Epub 2018 Nov 26.

Authors

Han Zou¹, Yumei Duan², Dongliang Wei³, Yiqian Zhang⁴, Jiacheng Dai⁵, Junzhi Li⁶, Xiaojie Li⁷, Jianhua Zhou⁸, Zhixiong Liu⁹, Zhongyuan Jin⁸, Zhou Zhang¹⁰, Yang Yu⁴, Zhongliang Hu¹¹

Affiliations

¹ Department of Eight-Grade Clinical Medicine, Xiangya Medical School, Central South University, Changsha 410008, China; Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha 410008, China.
² Department of Pathology, Xiangya Hospital, Central South University, Changsha 410008, China.
³ Xiangya School of Stomatology, Central South University, Changsha 410000, China.
⁴ Department of Eight-Grade Clinical Medicine, Xiangya Medical School, Central South University, Changsha 410008, China.
⁵ Center for Medical Genetics, School of Life Sciences, Central South University, Changsha 410078, China.
⁶ Department of Pathology, The First Affiliated Hospital of Xinjiang Medical University, Xinjiang Medical University, Urumqi 830054, China.
⁷ Department of Pathology, the First People's Hospital of Chenzhou, Chenzhou 423000, China.
⁸ Department of Pathology, Xiangya Hospital, Central South University, Changsha 410008, China; Department of Pathology, Xiangya Medical School, Central South University, Changsha 410013, China.
⁹ Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha 410008, China.
¹⁰ Burning Rock Biotech, Guangzhou 510300, China.
¹¹ Department of Pathology, Xiangya Hospital, Central South University, Changsha 410008, China; Department of Pathology, Xiangya Medical School, Central South University, Changsha 410013, China; Department of Pathology, Institute of Basic Medicine, Xinjiang Medical University, Urumqi 830011, China. Electronic address: huzhongliang@csu.edu.cn.

PMID: 30496796
DOI: 10.1016/j.humpath.2018.08.038

Abstract

Pleomorphic xanthoastrocytoma (PXA) is a rare central nervous system tumor occurring mostly in children and young adults. Next-generation sequencing of 295 cancer-related genes was used to investigate the molecular profiles of 13 cases of PXA. We found that BRAF V600E (5/13; 38%), FANCA/D2/I/M (5/13; 38%), PRKDC (4/13; 31%), NF1 (3/13; 23%), and NOTCH2/3/4 (3/13; 23%) alterations were the most frequent somatic gene mutations. However, neither PTEN nor EGFR mutation, which is frequently present in glioblastoma, was detected. The KRAS mutation in PXA is reported for the first time in these tumors. Microsatellite stability was present in all cases. Because mutations of FANCA and BRAF and copy number variations of CDKN2A/B are more frequent in PXA than in glioblastoma, they might be used to distinguish the 2 tumors. The MAPK pathway is involved in the pathogenesis of PXA and may be an effective target for treatment.

Keywords: MAPK pathway; Microsatellite stability; Molecular feature; Next-generation sequencing; Pleomorphic xanthoastrocytoma.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Astrocytoma / genetics*
Astrocytoma / metabolism
Astrocytoma / pathology
Brain Neoplasms / genetics*
Brain Neoplasms / metabolism
Brain Neoplasms / pathology
Child
Child, Preschool
DNA Copy Number Variations
DNA Mutational Analysis
Fanconi Anemia Complementation Group A Protein / genetics
Fanconi Anemia Complementation Group A Protein / metabolism
Female
Humans
Male
Microsatellite Instability
Middle Aged
Mutation*
Proto-Oncogene Proteins B-raf / genetics
Proto-Oncogene Proteins B-raf / metabolism
Proto-Oncogene Proteins p21(ras) / genetics
Proto-Oncogene Proteins p21(ras) / metabolism

Substances

Fanconi Anemia Complementation Group A Protein
KRAS protein, human
BRAF protein, human
Proto-Oncogene Proteins B-raf
Proto-Oncogene Proteins p21(ras)