Case Report: A Rare Co-Occurrence of Two Mutations in the CALR Gene Causing MPN

CALR基因中兩個罕見突變同時發生導致MPN

根據文獻，約70% JAK2和MPL突變陰性的原發性血小板增多症和原發性骨髓纖維化患者存在CALR基因突變。由52 bp缺失引起p.L367fs*46及由5 bp插入產生p.K385fs*47兩種常見的變異，約佔所有CALR突變80%以上。然而，CALR基因共存兩個突變的情況很少見，其與臨床疾病的關聯以及對患者預後的影響迄今尚未曾被報導過。我們在此報告一診斷為ET的病例，其CALR中存在兩個突變：p.Ala382Glnfs*48 (c.1144delG)和p.Asp408Metfs*22 (c.1222delG)，並且臨床出現嚴重的相關疾病表現。更重要的是這兩個點位的突變我們並未發現在COSMIC (https://cancer.sanger.ac.uk/cosmic)或HGMD (http://www.hgmd.cf.ac.uk) databases有被登記過。

Somatic mutations of the CALR gene have been reported in about 70% of patients with essential thrombocythemia (ET) and primary myelofibrosis (PMF) who are negative for JAK2 and MPL mutations. Most of the CALR mutations characterized to date consist of heterozygous mutations in exon 9 of the gene. There were two common variants, and together they comprise more than 80% of all CALR mutations: L367fs*46 (type 1), resulting from a 52-bp deletion; and K385fs*47 (type 2), which resulted from a 5-bp insertion. However, the coexistence of two mutations in the CALR gene is rarely encountered, and its association with the clini cal behavior of the disease and its impact on patient outcomes have not been reported so far. We herein report a case diagnosed with ET that has two coexisting mutations: Ala382Glnfs*48 (c.1144d elG) and Asp408Metfs*22 (c.1222delG) in CALR and had severe disease manifestations at presentat ion. More importantly, the two novel exons 9 CALR mutations that we discovered have not yet been registered in the COSMIC (https://cancer.sanger.ac.uk/cosmic) or HGMD (http://www.hgmd.cf.ac.uk) databases, to the best of our knowledge.