Advancing precision diagnostics in oncology: VHIO to co-develop novel Next-Next Generation Sequencing

 • Six Barcelona-based research entities to develop Next-Next Generation Sequencing (NNGS) platform to advance cancer and infectious disease diagnostics

• Pharmaceutical company Roche selects the Vall d´Hebron Hospital Campus Barcelona as the first ever test-center for novel mass-sequencing platform

• This new platform will spur development of NNGS diagnostic applications of cancer and infectious diseases. In oncology, platform validation and development will be carried out in collaboration with IDIBELL for hereditary cancer and by VHIO and the Hospital del Mar for non-hereditary cancers.

Roche Diagnostics last week announced the launch of its Next-Next Generation Personalized Medicine Platform to be implemented and developed in partnership by the Vall d´Hebron Institute of Oncology (VHIO), Vall d´Hebron Institute of Research (VHIR), Vall d´Hebron University Hospital (HUVH), IDIBELL-Bellvitge Biomedical Research Institute (IDIBELL-ICO), Hospital del Mar Medical Research Institute (IMIM), and the IrsiCaixa Institute for AIDS Research – located in the Germans Trias i Pujol Hospital.

The main objective of the project is to drive the development of powerful diagnostics based on the high-throughput massive sequencing of genomic systems of high variability such as viruses, bacteria, and tumor cells. The validation and routine clinical application of this technology will render cancer medicine more precise by providing optimal diagnosis and therapy for the right patient in the right dose at the right time.

The three year project supported through an investment of over €8 million, is financed by the Centre for the Development of Industrial Technology (CDTI), of the Spanish Ministry of Economy and Competitiveness, and will pilot pioneering single molecule real time (SMRT)-NNG Sequencing technology that, once validated at the VHIR, will join VHIO´s suite of cutting-edge technology platforms and also be incorporated at the other participating centers.

Application of Next-Next Generation Sequencing (NNGS) technology

Roche´s Next-Next Generation Personalized Medicine Platform employs SMRT technology that facilitates the sequencing of up to 8 human genomes in a one shot analysis. In addition to saving time, this powerful approach will enable identification of genome repetitions and thus widen the scope of all studies in this field.

The project comprises two main areas: the development of NNGS applications for the diagnosis of infectious diseases (virus/bacteria) in collaboration with VHIR-HUVH and IrsiCaixa, and the advancement of these technologies for cancer diagnostics led by IDIBELL for hereditary cancer and by VHIO in collaboration with the Hospital del Mar Medical Research Institute (IMIM) for non-hereditary tumors.

Applications of Next-Next Generation Sequencing in oncology

Cancer is an extremely heterogeneous and complex disease. Thanks to avant-garde genomic sequencing techniques coupled with preclinical and clinical discovery, more than 500 genes have been evidenced as being implicated in cancer development.

The current era of molecular cancer diagnostics necessitates the integration of genetic tests in routine clinical practice for better guided, more precise selection of therapy. These tests detect genetic alterations in patient tumor samples which provide vital clinical insights for disease prognosis as well as treatment selection for individual patients. Each of the Next-Next Generation Personalized Medicine Platform partners will devise a series of clinical applications for the successful integration and development of the technology for the benefit of patients.

VHIO: driving development of Next-Next Generation Sequencing in oncology

Leading the development of three applications, VHIO will join the platform in 2017.

“Given the tremendous potential of this novel technology, we are devoted to leading the necessary research that will both promote the development and validation of this approach in oncology as well as pave the way for its successful application in routine clinical practice”, says Ana Vivancos, Principal Investigator of VHIO´s Cancer Genomics Group.

The first application will involve the development of a protocol to capture genomic regions of interest for direct sequencing without intermediate amplification. This application, facilitated by NNGS technology, will for the first time determine nucleotide patterns in cancer genomes directly. Its clinical application will establish the state of methylation of cytosines in the MGMT promoter which determines the response of brain tumors (Glioblastoma Multiforme) to treatment with the oral chemotherapy drug temozolomide.


“Through this protocol design coupled with novel sequencing technology we aim to directly sequence tumor DNA for the very first time without having to carry out PCR sequencing that deletes the copy process of epigenetic marks found in DNA that, we suspect, are vitally important in better understanding tumor biology”
, remarks Ana Vivancos.

The second phase, to be validated at the Hospital del Mar Medical Research Institute, consists of developing an application to detect microsatellite instability (MSI) in patient tumor samples. MSI status is an important prognostic factor in certain tumor types including colorectal and uterine cancer. Microsatellites are sections of DNA consisting of short tandem repeats. MSI state is a consequence of disruption to DNA repair in tumors that then accumulate a high number of mutations. Currently there are no MSI tests available for the ultrasequencing of short read lengths, but this new Roche-NNGS platform will facilitate the read lengths necessary to be applied to this field.

Thirdly, a multiplex PCR panel test (Amplicon-seq) will be developed for the evaluation of BRCA1/2 mutation status in ovarian tumor samples. Representing a significant advance in technology, mutations will be detected in these genes through analysis of paraffin embedded patient tumor samples. Importantly, BRCA1/2 mutations in ovarian cancer correlate with response to the targeted therapy olaparib.

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For more information surrounding VHIO´s participation in the NNGS platform please contact: Amanda Wren, Director of Communications, Vall d´Hebron Institute of Oncology (VHIO), Tel: +34 695 207 886, Email: awren@vhio.net.

NNGS-ROCHE platform representatives announcing the project launch: Hospital del Mar, IDIBELl, VHIR, IRSICAIXA y VHIO

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