Comprehensive Analysis of Acquired Genetic Variants and Their Prognostic Impact in Systemic Mastocytosis

Cancers

Alberto Orfao¹  Javier I. Muñoz-González¹  Andrés C. García-Montero¹  Oscar González-López¹  Iván Álvarez-Twose² 

[1] Cancer Research Center (IBMCC, USAL/CSIC), Department of Medicine, Universidad de Salamanca, Biomedical Research Institute of Salamanca and Spanish Network on Mastocytosis (REMA), 37007 Salamanca, Spain;Centro de Investigación Biomédica en Red Cáncer (CIBERONC), 28029 Madrid, Spain;

关键词: systemic mastocytosis;    prognostic;    mutations;    KIT;    D816V;    ASXL1;   

DOI  :  10.3390/cancers14102487

来源: DOAJ

【 摘 要 】

Systemic mastocytosis (SM) is a rare clonal haematopoietic stem cell disease in which activating KIT mutations (most commonly KIT D816V) are present in virtually every (>90%) adult patient at similar frequencies among non-advanced and advanced forms of SM. The KIT D816V mutation is considered the most common pathogenic driver of SM. Acquisition of this mutation early during haematopoiesis may cause multilineage involvement of haematopoiesis by KIT D816V, which has been associated with higher tumour burden and additional mutations in other genes, leading to an increased rate of transformation to advanced SM. Thus, among other mutations, alterations in around 30 genes that are also frequently mutated in other myeloid neoplasms have been reported in SM cases. From these genes, 12 (i.e., ASXL1, CBL, DNMT3A, EZH2, JAK2, KRAS, NRAS, SF3B1, RUNX1, SF3B1, SRSF2, TET2) have been recurrently reported to be mutated in SM. Because of all the above, assessment of multilineage involvement of haematopoiesis by the KIT D816V mutation, in the setting of multi-mutated haematopoiesis as revealed by a limited panel of genes (i.e., ASXL1, CBL, DNMT3A, EZH2, NRAS, RUNX1 and SRSF2) and associated with a poorer patient outcome, has become of great help to identify SM patients at higher risk of disease progression and/or poor survival who could benefit from closer follow-up and eventually also early cytoreductive treatment.

【 授权许可】

Unknown