Abstract
Multiple myeloma (MM) is a cancer of antibody-making plasma cells. It frequently harbors alterations in DNA and chromosome copy numbers, and can be divided into two major subtypes, hyperdiploid (HMM) and non-hyperdiploid multiple myeloma (NHMM). The two subtypes have different survival prognosis, possibly due to different but converging paths to oncogenesis. Existing methods for identifying the two subtypes are fluorescence in situ hybridization (FISH) and copy number microarrays, with increased cost and sample requirements. We hypothesize that chromosome alterations have their imprint in gene expression through dosage effect. Using five MM expression datasets that have HMM status measured by FISH and copy number microarrays, we have developed and validated a K-nearest-neighbor method to classify MM into HMM and NHMM based on gene expression profiles. Classification accuracy for test datasets ranges from 0.83 to 0.88. This classification will enable researchers to study differences and commonalities of the two MM subtypes in disease biology and prognosis using expression datasets without need for additional subtype measurements. Our study also supports the advantages of using cancer specific characteristics in feature design and pooling multiple rounds of classification results to improve accuracy. We provide R source code and processed datasets at www.ChengLiLab.org/software.
Highlights
Multiple myeloma (MM) is a plasma cell malignancy characterized by complex and heterogeneous cytogenetic abnormalities [1]
Using fluorescence in situ hybridization (FISH), multiple myeloma is divided into hyperdiploid multiple myeloma (HMM) and non-hyperdiploid multiple myeloma (NHMM) [4,5]
Multiple myeloma is a malignant cancer of bone marrow plasma cells
Summary
Multiple myeloma (MM) is a plasma cell malignancy characterized by complex and heterogeneous cytogenetic abnormalities [1]. In the U.S, multiple myeloma is the second most common hematological malignancy and constitutes 1% of all cancers [2]. Aneuploidy, defined as copy number changes of chromosomes or regions, is a common feature of many human cancers including MM [3]. Common chromosome amplification and deletion events can be used as a feature to subdivide multiple myeloma into two subtypes. 55–60% of patients have the hyperdiploid karyotype, with trisomies of eight specific chromosomes, including chromosome 3, 5, 7, 9, 11, 15, 19 and 21 [6,7]. The remaining cases form the nonhyperdiploid group, frequently involving translocations and hemizygous deletion of chromosome 13
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