A Rare PALB2 Germline Variant Causing G2/M Cell Cycle Arrest is Associated with Isolated Myelosarcoma in Infancy

Overview

Journal Mol Genet Genomic Med

Specialty Genetics

Date 2021 Aug 12

PMID 34382369

Citations 3

Authors

Angelina Beer

Ricardo Beck

Anne Schedel

Malte von Bonin

Jorn Meinel

Ulrike Anne Friedrich

Maria Menzel

Meinolf Suttorp

Sebastian Brenner

Guido Fitze

Bjorn Lange

Ralf Knofler

Julia Hauer

Franziska Auer

Affiliations

Soon will be listed here.

Abstract

Background: Isolated myelosarcoma of infancy is a rare presentation of acute myelogenous leukaemia (AML). Because of its rarity and early onset in infancy underlying genetic predisposition is potentially relevant in disease initiation.

Methods And Results: We report an oncologic emergency in an infant with thoracic and intraspinal aleukaemic myeloid sarcoma causing acute myelon compression and lower leg palsy. Whole-exome sequencing of the patient's germline DNA identified a rare PALB2 (OMIM 610355) variant (p.A1079S), which is located in a domain critical for the gene's proper function within the homology-directed repair pathway. In line with potential DNA damage repair defects mediated by the PALB2 deregulation, the patient's fibroblasts showed increased sensitivity towards radiation and DNA intercalating agents.

Conclusion: Therefore, we suggest PALB2 p.A1079S as a pathogenic variant potentially contributing to the here observed patient phenotype.

Citing Articles

A case report of malignant neuroectodermal tumor of the gastrointestinal tract without common gene fusion in a soft tissue tumor.

Liu Z, Zhou B, Zhao Y, Yu M, Liang J, Li Y J Gastrointest Oncol. 2022; 13(3):1489-1498.

PMID: 35837202 PMC: 9274067. DOI: 10.21037/jgo-22-387.

A Case of Isolated Myeloid Sarcoma Associated With Germline T790M Variant: The Importance of Recognizing Potential Germline Variants on Somatic Tumor Sequencing Panels.

Walker M, Folstad M, Smith-Simmer K, Reinig E, Nadiminti K, Lovrien L J Hematol. 2022; 11(2):71-76.

PMID: 35573754 PMC: 9076140. DOI: 10.14740/jh983.

A rare PALB2 germline variant causing G2/M cell cycle arrest is associated with isolated myelosarcoma in infancy.

Beer A, Beck R, Schedel A, von Bonin M, Meinel J, Friedrich U Mol Genet Genomic Med. 2021; 9(9):e1746.

PMID: 34382369 PMC: 8457705. DOI: 10.1002/mgg3.1746.

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Beer A, Beck R, Schedel A, von Bonin M, Meinel J, Friedrich U . A rare PALB2 germline variant causing G2/M cell cycle arrest is associated with isolated myelosarcoma in infancy. Mol Genet Genomic Med. 2021; 9(9):e1746. PMC: 8457705. DOI: 10.1002/mgg3.1746. View