Mutations that Distinguish Benign from Malignant Plasma Cell Neoplasams

 描述（由申请人提供）多发性骨髓瘤（MM）是一种骨髓浆细胞癌症，在美国每年导致超过一万人死亡。MGUS非常常见（4%的成年人），总体而言每年进展为MM的风险较低（约1-2%）。我们无法预防进展为MM，目前建议每年对MGUS患者进行随访。不幸的是，大多数患者在年度就诊之间进展为MM，遭受MM的并发症，包括骨病、贫血和肾功能不全。MM中发现的大多数遗传变化也存在于MGUS中，然而最近我们发现了可能驱动MGUS进展为MM的候选基因突变，可能提供有用的遗传生物标志物。该项目将探索MGUS和MM患者之间的遗传差异，目的是了解进展的遗传机制，改进我们的风险预测模型，并预防MGUS患者遭受MM并发症。

 DESCRIPTION (provided by applicant) Multiple myeloma (MM) is a cancer of bone marrow plasma cells that results in over ten thousand deaths a year in the USA.It is always preceded by a pre-malignant phase called monoclonal gammopathy of undetermined significance (MGUS). MGUS is very common (4% of adults), and overall has a low risk (~1-2%) each year of progressing to MM. We are unable to prevent the progression to MM, and currently recommend that patients with MGUS be followed annually. Unfortunately most patients progress to MM between the annual visits, sufferring from the complications of MM that include bony disease, anemia, and renal insufficiency. Most of the genetic changes identified in MM are also present in MGUS, however recently we have identified candidate genetic mutations that may drive the progression of MGUS to MM, potentially providing a useful genetic biomarker. This project will explore the genetic differences between patients with MGUS and MM with the goal of understanding the genetic mechanisms of progression and improving our risk prediction models, and preventing MGUS patients from suffering the complications of MM.