Misidentification of MLL3 and other mutations in cancer due to highly homologous genomic regions.

Autor: Bowler TG; Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY, USA., Pradhan K; Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY, USA., Kong Y; Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY, USA., Bartenstein M; Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY, USA., Morrone KA; Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY, USA., Sridharan A; Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY, USA., Kessel RM; Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY, USA., Shastri A; Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY, USA., Giricz O; Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY, USA., Bhagat TD; Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY, USA., Gordon-Mitchell S; Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY, USA., Rohanizadegan M; Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY, USA., Hooda L; Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY, USA., Datt I; Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY, USA., Przychodzen BP; Cleveland Clinic, Cleveland, OH, USA., Parmar S; MD Anderson Cancer Center, Houston, TX, USA., Maqbool S; Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY, USA., Maciejewski JP; Cleveland Clinic, Cleveland, OH, USA., Steidl U; Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY, USA., Greally JM; Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY, USA., Verma A; Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY, USA.
Jazyk: angličtina
Zdroj: Leukemia & lymphoma [Leuk Lymphoma] 2019 Dec; Vol. 60 (13), pp. 3132-3137. Date of Electronic Publication: 2019 Jul 10.
DOI: 10.1080/10428194.2019.1630620
Abstrakt: The MLL3 gene has been shown to be recurrently mutated in many malignancies including in families with acute myeloid leukemia. We demonstrate that many MLL3 variant calls made by exome sequencing are false positives due to misalignment to homologous regions, including a region on chr21, and can only be validated by long-range PCR. Numerous other recurrently mutated genes reported in COSMIC and TCGA databases have pseudogenes and cannot also be validated by conventional short read-based sequencing approaches. Genome-wide identification of pseudogene regions demonstrates that frequency of these homologous regions is increased with sequencing read lengths below 200 bps. To enable identification of poor quality sequencing variants in prospective studies, we generated novel genome-wide maps of regions with poor mappability that can be used in variant calling algorithms. Taken together, our findings reveal that pseudogene regions are a source of false-positive mutations in cancers.
Databáze: MEDLINE
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