Ashby Cody, Tytarenko Ruslana G, Wang Yan, Weinhold Niels, Johnson Sarah K, Bauer Michael, Wardell Christopher P, Schinke Carolina, Thanendrarajan Sharmilan, Zangari Mauricio, van Rhee Frits, Davies Faith E, Sawyer Jeffrey R, Morgan Gareth J, Walker Brian A
Myeloma Center, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
Oncotarget. 2019 Jan 22;10(7):732-737. doi: 10.18632/oncotarget.26589.
Hyperhaploid multiple myeloma is a rare numerical aberration group defined by a range of 24-34 chromosomes, which is associated with a poor prognosis with a 5-year survival rate of 23%. Hyperhaploid patient samples (n=8) were sequenced and copy number and mutations identified. Samples had a median of 13 monosomies (range 12-14), which in general were those not associated with trisomies in hyperdiploid samples. The chromosomes traditionally trisomic in hyperdiploid myeloma were disomic in hyperhaploid myeloma with retention of heterodisomy. We examined the hyperhaploid samples for frequently mutated genes and found that 8/8 (100%) hyperhaploid samples had a mutation in , exceeding the overall rate of mutation in newly diagnosed patients (5.5%), indicating an oncogenic dependency in this group. All samples with mutation also had monosomy of chromosome 17, indicating bi-allelic inactivation of . As such, this high risk group is part of double-hit myeloma.
超单倍体多发性骨髓瘤是一种罕见的染色体数目异常类型，其染色体数目范围为24 - 34条，与预后不良相关，5年生存率为23%。对超单倍体患者样本（n = 8）进行测序，并鉴定拷贝数和突变情况。样本中单体的中位数为13条（范围为12 - 14条），这些单体通常是那些在超二倍体样本中不与三体相关的单体。在超二倍体骨髓瘤中传统上三体化的染色体在超单倍体骨髓瘤中为二体，且保留了异源二体性。我们检查了超单倍体样本中频繁突变的基因，发现8/8（100%）的超单倍体样本在 中有突变，超过了新诊断患者的总体突变率（5.5%），表明该组存在致癌依赖性。所有有 突变的样本也都有17号染色体单体，表明 的双等位基因失活。因此，这个高风险组是双打击骨髓瘤的一部分。
