Rapid identification of compound mutations in patients with Philadelphia-positive leukaemias by long-range next generation sequencing

European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)
R KastnerC Gabriel

Abstract

An emerging problem in patients with Philadelphia (Ph)-positive leukaemias is the occurrence of cells with multiple mutations in the BCR-ABL1 tyrosine kinase domain (TKD) associated with high resistance to different tyrosine kinase inhibitors. Rapid and sensitive detection of leukaemic subclones carrying such changes, referred to as compound mutations, is therefore of increasing clinical relevance. However, current diagnostic methods including next generation sequencing (NGS) of short fragments do not optimally meet these requirements. We have therefore established a long-range (LR) NGS approach permitting massively parallel sequencing of the entire TKD length of 933bp in a single read using 454 sequencing with the GS FLX+ instrument (454 Life Sciences). By testing a series of individual and consecutive specimens derived from six patients with chronic myeloid leukaemia, we demonstrate that long-range NGS analysis permits sensitive identification of mutations and their assignment to the same or to separate subclones. This approach also facilitates readily interpretable documentation of insertions and deletions in the entire BCR-ABL1 TKD. The long-range NGS findings were reevaluated by an independent technical approach in select ...Continue Reading

References

Dec 26, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Simona SoveriniUNKNOWN GIMEMA Working Party on Chronic Myeloid Leukemia
Jun 16, 2007·Leukemia Research·Raphael P M CurvoMiguel A M Moreira
Sep 15, 2007·Nature Reviews. Drug Discovery·Alfonso Quintás-CardamaJorge Cortes
Nov 4, 2009·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Michele BaccaraniUNKNOWN European LeukemiaNet
Oct 1, 2011·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·S PreunerT Lion
Jan 11, 2012·American Journal of Hematology·Mary AlikianLetizia Foroni
Oct 24, 2012·American Journal of Hematology·Elias Jabbour, Hagop Kantarjian
Jun 5, 2013·BMC Bioinformatics·Norbert NiklasChristian Gabriel

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Citations

Mar 8, 2016·British Journal of Haematology·Simona SoveriniGiovanni Martinelli
Sep 9, 2015·BMC Research Notes·Norbert NiklasChristian Gabriel
May 6, 2014·The Journal of Molecular Diagnostics : JMD·Sandra PreunerThomas Lion
Feb 24, 2015·Current Hematologic Malignancy Reports·Christopher A Eide, Thomas O'Hare
May 3, 2016·International Journal of Molecular Sciences·Sandra PreunerChristian Gabriel
May 31, 2017·British Journal of Cancer·Maribel Forero-CastroJesús-María Hernández-Rivas
Oct 4, 2016·Therapeutic Advances in Hematology·Justine Ellen Marum, Susan Branford
Sep 27, 2019·Frontiers in Oncology·Barbara IzzoSara Galimberti
Apr 2, 2016·The Oncologist·Simona SoveriniGiovanni Martinelli

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