정혜정 (National Institutes of Health) | 한빛사논문 > 한빛사

한빛사논문

조회94

National Institutes of Health

Acta Neuropathol., Oct 18 2024, 148 (1) | https://doi.org/10.1007/s00401-024-02803-0 MYB/MYBL1-altered gliomas frequently harbor truncations and non-productive fusions in the MYB and MYBL1 genes

Hye‑Jung Chung¹ · Sharika Rajan¹· Zhichao Wu¹· Christina K. Ferrone¹ · Mark Rafeld¹ · Ina Lee¹ · Jefrey Gagan¹ · Christopher Dampier¹ · Zied Abdullaev¹ · Manoj Tyagi¹· Patrick. J. Cimino² · Martha Quezado¹ · Kenneth Aldape¹

¹Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 10 Center Dr., Room 2S235, Bethesda, MD 20892, USA

²Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892, USA

Hye-Jung Chung and Sharika Rajan contributed equally.

^*Corresponding author: Kenneth Aldape

Abstract

Astrocytomas that harbor recurrent genomic alterations in MYB or MYBL1 are a group of Pediatric-type diffuse low-grade gliomas that were newly recognized in the 2021 WHO Classification of Tumors of the Central Nervous System. These tumors are described in the WHO classification as harboring fusions in MYB or MYBL1. In this report, we examine 14 consecutive cases in which a MYB or MYBL1 alteration was identified, each with diagnostic confirmation by genome-wide DNA methylation profiling (6 Angiocentric gliomas and 8 Diffuse astrocytomas, MYB- or MYBL1-altered), for their specific genomic alterations in these genes. Using RNA sequencing, we find productive in-frame fusions of the MYB or MYBL1 genes in only 5/14 cases. The remaining 9 cases show genomic alterations that result in truncation of the gene, without evidence of an in-frame fusion partner. Gene expression analysis showed overexpression of the MYB(L1) genes, regardless of the presence of a productive fusion. In addition, QKI, a recognized fusion partner common in angiocentric glioma, was generally up-regulated in these 14 cases, compared to a cohort comprising >1000 CNS tumors of various types, regardless of whether a genomic alteration in QKI was present. Overall, the results show that truncations, in the absence of a productive fusion, of the MYB(L1) genes can likely drive the tumors and have implications for the analysis and diagnosis of Angiocentric glioma and Diffuse astrocytoma, MYB- or MYBL1-altered, especially for cases that are tested on panels designed to focus on fusion detection.

논문정보

형식Research article
게재일2024년 10월 (BRIC 등록일 2024-11-06)
연구진국외 연구진
분야

댓글 작성 로그인

CV 열람하기

연락처 보기