Figure 2
Figure 2. Primary BL cases demonstrate recurrent alterations in ARID1A and MCL1. (A) Representation of ARID1A gene and mutations identified by sequencing. The 20 exons of ARID1A are represented in the green boxes. Diamonds represent deletion; triangles represent point mutation. In all 5 cases, the mutation was truncating. ARID indicates AT-rich interactive domain; LXXLL, leucine-rich motifs; nt, nucleotide; and UTR, untranslated region. (B) ARID1A protein expression in mutated and wild-type cases as determined by IHC. Cases B-6 and BL-17 have truncating mutations upstream to the antibody epitope and demonstrate decreased staining compared with cases lacking mutations. Case BL-27 has a mutation downstream of the antibody probe. (C) MCL1 pathway-altered cases as identified by sequencing. Five cases had a 1.8 to 3.1 copy gain of MCL1 relative to a diploid control, corresponding to a predicted 4-6 copies of MCL1 per tumor cells. One case had a mutation in FBXW7, a gene in the MCL1 pathway. (D) FISH for MCL1 using an MCL1 probe (red) and centromeric probe for chromosome 1 (green). A representative wild-type case (WT; left) and an amplified case (right) are shown. Amplified cases had 3-4 copies, but in some a signal was stronger, suggesting tandem duplication. (E) MCL1 protein expression was evaluated by immunohistochemistry. Quantitative analysis of MCL1 staining intensity in tonsil (n = 3), MCL1 WT (n = 24), and MCL1 amplified (n = 5) cases is shown. Error bars represent standard error of the mean. Unpaired t test was performed to evaluate statistical significance between expression in MCL1 WT and MCL1 amplified cases. (F) Representative normal and amplified cases are shown, as well as the pattern in a tonsil control showing stronger cytoplasmic expression in the follicles. Panels B and F, original magnification ×400 with 40× objective lens. Microscope: Olympus BX 41; camera: Olympus Q-COLOR3; software: QCapture Version 2.9.8.0 (Quantitative Imaging). Panel D, original magnification ×1000: Apochromatic 100× lens with 1.4 aperture; microscope: Olympus BX51; camera: Jai CV-A10CL; software: Cytovision Imaging Version 3.6 (Genetix).

Primary BL cases demonstrate recurrent alterations in ARID1A and MCL1. (A) Representation of ARID1A gene and mutations identified by sequencing. The 20 exons of ARID1A are represented in the green boxes. Diamonds represent deletion; triangles represent point mutation. In all 5 cases, the mutation was truncating. ARID indicates AT-rich interactive domain; LXXLL, leucine-rich motifs; nt, nucleotide; and UTR, untranslated region. (B) ARID1A protein expression in mutated and wild-type cases as determined by IHC. Cases B-6 and BL-17 have truncating mutations upstream to the antibody epitope and demonstrate decreased staining compared with cases lacking mutations. Case BL-27 has a mutation downstream of the antibody probe. (C) MCL1 pathway-altered cases as identified by sequencing. Five cases had a 1.8 to 3.1 copy gain of MCL1 relative to a diploid control, corresponding to a predicted 4-6 copies of MCL1 per tumor cells. One case had a mutation in FBXW7, a gene in the MCL1 pathway. (D) FISH for MCL1 using an MCL1 probe (red) and centromeric probe for chromosome 1 (green). A representative wild-type case (WT; left) and an amplified case (right) are shown. Amplified cases had 3-4 copies, but in some a signal was stronger, suggesting tandem duplication. (E) MCL1 protein expression was evaluated by immunohistochemistry. Quantitative analysis of MCL1 staining intensity in tonsil (n = 3), MCL1 WT (n = 24), and MCL1 amplified (n = 5) cases is shown. Error bars represent standard error of the mean. Unpaired t test was performed to evaluate statistical significance between expression in MCL1 WT and MCL1 amplified cases. (F) Representative normal and amplified cases are shown, as well as the pattern in a tonsil control showing stronger cytoplasmic expression in the follicles. Panels B and F, original magnification ×400 with 40× objective lens. Microscope: Olympus BX 41; camera: Olympus Q-COLOR3; software: QCapture Version 2.9.8.0 (Quantitative Imaging). Panel D, original magnification ×1000: Apochromatic 100× lens with 1.4 aperture; microscope: Olympus BX51; camera: Jai CV-A10CL; software: Cytovision Imaging Version 3.6 (Genetix).

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