Mayo Clinic Laboratory and Pathology Research Roundup: Aug. 8

The Research Roundup provides an overview of the past week’s research from Mayo Medical Laboratories consultants, including a featured article of the week, abstracts, and complete list of published studies and reviews.

Featured Abstracts

Genomic Characterization of High-Count MBL Cases Indicates That Early Detection of Driver Mutations and Subclonal Expansion are Predictors of Adverse Clinical Outcome

Leukemia-960x540High-count monoclonal B-cell lymphocytosis (MBL) is an asymptomatic expansion of clonal B cells in the peripheral blood without other manifestations of chronic lymphocytic leukemia (CLL). Yearly, 1% of MBLs evolve to CLL requiring therapy; thus being critical to understand the biological events that determine which MBLs progress to intermediate/advanced CLL. Mayo Clinic researchers performed targeted deep sequencing on 48 high-count MBLs, 47 of them with 2-4 sequential samples analyzed, exploring the mutation status of 21 driver genes and evaluating clonal evolution. The team found somatic non-synonymous mutations in 52% MBLs at the initial time point analyzed, including 25% with >1 mutated gene. In cases that subsequently progressed to CLL, mutations were detected 41 months prior to progression. Excepting NOTCH1, TP53, and XPO1, which showed a lower incidence in MBL, genes were mutated with a similar prevalence to CLL, indicating the early origin of most driver mutations in the MBL/CLL continuum. MBLs with mutations at the initial time point analyzed were associated with shorter time-to-treatment (TTT). Furthermore, MBLs showing subclonal expansion of driver mutations on sequential evaluation had shorter progression time to CLL and shorter TTT. These findings support that clonal evolution has prognostic implications already at the pre-malignant MBL stage, anticipating which individuals will progress earlier to CLL. The study was published in Leukemia

Custom Gene Capture and Next-Generation Sequencing to Resolve Discordant ALK Status by FISH and IHC in Lung Adenocarcinoma

lung-cancer-960x540Mayo Clinic researchers performed a genomic study in lung adenocarcinoma cases with discordant anaplastic lymphoma receptor tyrosine kinase gene (ALK) status by fluorescent in situ hybridization (FISH) and immunohistochemical (IHC) analysis. ALK FISH results appeared to be false-positive in three of four FISH-positive/IHC-negative cases, whereas no false-negative ALK FISH case was identified among 12 ALK FISH-negative/IHC-positive cases by ALK1 clone, which was in keeping with the concordant FISH-negative/IHC-negative status by D5F3 clone. The targeted whole gene capture approach using formalin-fixed paraffin embedded samples was effective for detecting rearrangements involving ALK and other actionable oncogenes. The study was published in the Journal of Thoracic Oncology.

Published to PubMed This Week



Brent Westra is a Marketing Segment Manager at Mayo Clinic Laboratories. He leads marketing strategies for product management and specialty testing along with new media innovations. Brent has worked at Mayo Clinic since 2011.