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Roche 454 Sequencing Systems Successfully Resolve Genetic Mutations in Blood Cancer Cases

Published: Thursday, December 13, 2012
Last Updated: Thursday, December 13, 2012
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International study presented at ASH Meeting demonstrates the potential of 454 Sequencing Systems to comprehensively characterize an individual’s blood cancer type to guide personalized therapy decisions.

At the American Society of Hematology Meeting (ASH) Roche has announced the presentation of results from the large scale study IRON-II through an international research consortium.

Based on next generation 454 Sequencing Systems from Roche, the study aims to characterize selected genes in individuals with a wide range of hematological malignancies.

The consortium of 26 laboratories from 13 countries in Europe and Asia performed comprehensive analysis of 74 genes in individuals with acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic lymphatic leukemia (CLL), chronic myelogenous leukemia (CML), myelodysplastic syndromes (MDS), and myeloproliferative neoplasms (MPN).

The results from over 4,000 cases demonstrate that the highly advanced technology supports the comprehensive molecular characterization of hematological malignancies with high sensitivity and specificity, with the future prospect of guiding more personalized treatment decisions.

The study is one of dozens of abstracts and talks using 454 Sequencing Systems presented at the ASH meeting this week.

Researchers from the MLL Munich Leukemia Laboratory, pioneering the adoption of next-generation sequencing to profile blood cancers, are leading the international consortium.

Earlier this year, Roche launched a set of sequence-based primer sets co-developed with the MLL for deep genetic variation detection in the TET2, CBL, KRAS, and RUNX1 genes using the GS FLX and GS Junior Systems.

The current study is an extension of the previous IRON study which demonstrated the robustness, precision and reproducibility of next generation sequencing with 454 Sequencing Systems for characterization of key genes associated with leukemia.

It broadens the set of genes from 3 to 74 with a new expanded set of investigative primer plates.

“We are particularly pleased with the performance of the Roche assays in combination with the high quality long read length of the 454 Sequencing Systems. This is the only technology that allows us to resolve complex variations in genes such as RUNX1 or CEBPA and enables us to address questions such as landmark analyses in various mutated genes in hematological malignancies and the development of future prognostic models,” said Dr. Alexander Kohlmann, Head of the Next Generation Sequencing Group at the MLL and coauthor of 28 studies presented at this year’s conference.

Kohlmann continued, “One key aspect of the IRON-II study is that we now achieved to standardize gene content via amplicon-based deep-sequencing assays across hematological expert laboratories, including the bioinformatic analysis approaches.”

In addition to the consortium results, the MLL Munich Leukemia Laboratory presented novel sequencing data on various disease types including the role of TP53 and CEBPA mutations in AML, or SF3B1 and NOTCH1 mutations in CLL.

“By applying this novel technology we are now in a position to challenge existing schemes for classification and scoring," said Prof. Torsten Haferlach, cofounder and CEO of the MLL. “We can begin to integrate molecular information into more biologically driven models. Ultimately, this could allow us to individualize our approach to treat our patients.”

“We are pleased with the results of the international study, which continues to evaluate the unique value of 454 Sequencing Systems in blood cancer research,” said Thomas Schinecker, President of 454 Life Sciences, a Roche Company.

Schinecker continued, “We are strongly supporting the community with the development of standardized gene panels for molecular characterization of hematological malignancies, which is an important step towards future routine clinical use.”


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