• Molecular characterization of myeloma requires isolation of malignant plasma cells, which is currently hampered by the instability of CD138.• We identified CD319 and CD269 as robust replacements for CD138, facilitating molecular diagnostics in myeloma.Molecular characterization of malignant plasma cells is increasingly important for diagnostic and therapeutic stratification in multiple myeloma. However, the malignant plasma cells represent a relatively small subset of bone marrow cells, and need to be enriched prior to analysis. Currently, the cell surface marker CD138 (SDC1) is used for this enrichment, but has an important limitation in that its expression decreases rapidly after sampling. Seeking alternatives to CD138, we performed a computational screen for myeloma plasma cell markers and systematically evaluated 7 candidates. Our results conclusively show that the markers CD319 (SLAMF7/CS1) and CD269 (TNFRSF17/BCMA) are considerably more robust than CD138 and enable isolation of myeloma plasma cells under more diverse conditions, including the samples that have been delayed or frozen.Our results form the basis of improved procedures for characterizing cases of multiple myeloma in clinical practice. (Blood. 2014;123(9):1336-1340 IntroductionMultiple myeloma (MM) is characterized by the uncontrolled, clonal growth of plasma cells in the bone marrow. As our knowledge increases about the genetic basis of MM, and new therapeutic options are being developed, molecular characterization of MM plasma cells (MMPCs) is becoming increasingly important for subclassification, prognostication, and treatment stratification.

Wilms tumor is the most common pediatric renal neoplasm, but few molecular prognostic markers have been identified for this tumor. Somatic deletion in the long arm of chromosome 16 (16q) is known to predict a less favorable outcome in Wilms tumor, but the underlying molecular mechanisms are not known. We show that 16q deletions are typically confined to immature anaplastic-blastic tumor elements, while deletions are absent in maturing tumor components. The smallest region of deletion overlap mapped to a 1.8-Mb segment containing the IRXB gene cluster including IRX3, IRX5, and IRX6, of which IRX3 is a recently identified regulator of tubular maturation during nephrogenesis. Tumors with 16q deletion showed a lower overall mRNA expression of IRXB genes, and 16q-deleted tumor cells failed to express IRX3 while it was expressed in differentiating tubular tumor elements with intact 16q. Consistent with a role for IRX3 in tubular differentiation, gene sets linked to Notch signaling, Rho signaling, and ion channel activity were enriched in tumors with high IRX3 expression, while WTs with low expression were enriched for gene sets linked to cell cycle progression. Wilms tumor accounts for more than 95% of kidney tumors in children. The majority of patients receiving modern multimodal therapy are cured, but 10 to 15% still die of disease.1 Histologically, most WTs mimic the fetal developing kidney in which immature cells of the metanephric mesenchyme differentiate into stromal and epithelial elements, the latter of which ultimately give rise to the nephronic tubules and glomeruli.2 The notion that Wilms tumor originates from pluripotent immature cells is supported by its characteristic triphasic histology, including blastemal, epithelial, and stromal components. The blastema consists of undifferentiated mesenchymal cells, resembling the metanephric mesenchyme, while the epithelial component might show different degrees of differentiation, including primitive tubular and glomeruloid formations. Gene expression studies have provided additional evidence for the hypothesis that Wilms tumor results from a differentiation block in embryonic kidney formation; genes overexpressed in Wilms tumor are also

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