Sequencing systems resolve genetic mutations in over 4000 blood cancer cases

At the 2012 American Society of Hematology (ASH) Annual Meeting, Roche 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 characterise selected genes in individuals with a wide range of haematological malignancies. The consortium of 26 laboratories from 13 countries in Europe and Asia performed comprehensive analyses of 74 genes in individuals with acute myeloid leukaemia (AML), acute lymphoblastic leukaemia (ALL), chronic lymphatic leukaemia (CLL), chronic myelogenous leukaemia (CML), myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN).

The results from over 4000 cases demonstrate that the technology supports the comprehensive molecular characterisation of haematological malignancies with high sensitivity and specificity, with the future prospect of guiding more personalised treatment decisions. The study was one of dozens of abstracts and talks using 454 Sequencing Systems presented at the ASH meeting.

Researchers from the MLL Munich Leukaemia Laboratory, pioneering the adoption of next-generation sequencing to profile blood cancers, are leading the international consortium. Earlier in 2012, 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 characterisation of key genes associated with leukaemia. It broadens the set of genes from three 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 co-author of 28 studies presented at the conference.

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

In addition to the consortium results, the MLL Munich Leukaemia 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 Professor Torsten Haferlach, co-founder and CEO of the MLL. “We can begin to integrate molecular information into more biologically driven models. Ultimately, this could allow us to individualise 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. “We are strongly supporting the community with the development of standardised gene panels for molecular characterisation of haematological malignancies, which is an important step towards future routine clinical use.”