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BCR‐ABL1‐like B‐Acute Lymphoblastic Leukemia (B‐ALL) is a subset of B‐ALL with a poor prognosis that is found in all age groups. Definitive identification of these patients is difficult in routine clinical practice as gene expression profiling, the gold standard test, is not widely available. Comprehensive genomic profiling performed on 450 patients with extensive fusion profiling revealed a wide range of genomic alterations which were consistent with a classification of BCR‐ABL1‐like B‐ALL in 29% of cases. This manuscript highlights a clinically available alternative method for identifying a large subset of patients with BCR‐ABL1‐like B‐ALL. BCR‐ABL1‐like B‐lymphoblastic leukemia, also termed Philadelphia‐like B‐acute lymphoblastic leukemia (Ph‐like B‐ALL), shares a gene expression profile similar to BCR‐ABL1‐positive B‐ALL1 but lacks BCR‐ABL1 fusion. Because Ph‐like status confers a poor prognosis, identification of Ph‐like B‐ALL cases is important. This brief communication reports 450 cases of B‐ALL evaluated by genomic profiling. [ABSTRACT FROM AUTHOR]

Introduction: In this study, we sought to further characterize ROS1 protein expression in solid tumors with the complete spectrum of ROS1 genomic alterations., Methods: ROS1 immunohistochemistry (IHC) was performed using the ROS1 (SP384) class I assay per manufacturer's instructions on a variety of solid tumors (n = 32) with known ROS1 genomic alterations. Genomic alterations included fusions (n = 17), gene amplifications (n = 10), and short-variant mutations (n = 11)., Results: Of the 32 cases with ROS1 IHC results, 100% (11 of 11) with canonical ROS1 fusions were positive for ROS1 IHC. Among noncanonical ROS1 fusions, only two (of five) cases with SQSTM1-ROS1 and RDX-ROS1 fusions were positive for ROS1 IHC whereas PTPRK - ROS1 (two) and TTC28-ROS1 fusions were negative for ROS1 IHC. One sample with a canonical ROS1 fusion and co-occurring ROS1 resistance mutation (6094G>A, p.G2032R) was positive for ROS1 IHC. A total of 10% (one of 10) of ROS1 amplified tumors were positive for ROS1 IHC. None of the cases (zero of five) with ROS1 short-variant mutations were positive for ROS1 protein expression., Conclusions: These findings suggest that if ROS1 IHC was used as a screening tool for ROS1 fusion, a subset of fusion-negative tumors will reveal positive IHC staining highlighting the value of reflexing to genomic profiling to confirm the presence of a targetable fusion-driver before the initiation of therapy. In addition, the ability of comprehensive genomic profiling to detect ROS1 resistance mutations will be important for clinical decision making., (© 2020 The Authors.)