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Detection of Rare Genomic Variants from Pooled Sequencing Using SPLINTER
Published on: June 23, 2012
An assessment of the effect of haemoglobin variants on detection by faecal immunochemical tests
Magdalen Rr Carroll1,2, Cerin John1,2, Debbie Mantio3
11 NHS Bowel Cancer Screening Programme Southern Hub, Royal Surrey County Hospital, Guildford, UK.
Background Faecal immunochemical tests (FIT) for haemoglobin (Hb) are being used in the investigation of colorectal cancer. These tests use antibodies raised to the globin moiety of human Hb. Where the globin structure is abnormal or reduced, it is possible that antibody binding, and thus Hb-detection may be affected. Methods Lysates prepared from whole blood samples of patients with known variants were diluted in manufacturer-specific buffer to 10, 100 and 500 μg Hb/g faeces. These samples were analysed on four FIT analysers and the results compared with samples with no known variant present (normal samples). Results The results from this study show that of 20 variants tested, three showed a decrease in detection by all four analysers. These were β-thalassaemia major and two fetal cord blood samples. Conclusions Of 20 common Hb variants studied, 17 did not affect detection of Hb by the FIT systems tested. Hb variants leading to a reduction in the presence of a globin chain caused a reduction in Hb detection; in such cases, cancers could be missed.
Background Faecal immunochemical tests (FIT) for haemoglobin (Hb) are being used in the investigation of colorectal cancer. These tests use antibodies raised to the globin moiety of human Hb. Where the globin structure is abnormal or reduced, it is possible that antibody binding, and thus Hb-detection may be affected. Methods Lysates prepared from whole blood samples of patients with known variants were diluted in manufacturer-specific buffer to 10, 100 and 500 μg Hb/g faeces. These samples were analysed on four FIT analysers and the results compared with samples with no known variant present (normal samples). Results The results from this study show that of 20 variants tested, three showed a decrease in detection by all four analysers. These were β-thalassaemia major and two fetal cord blood samples. Conclusions Of 20 common Hb variants studied, 17 did not affect detection of Hb by the FIT systems tested. Hb variants leading to a reduction in the presence of a globin chain caused a reduction in Hb detection; in such cases, cancers could be missed.
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