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Oesophageal cancer clinical and molecular stratification (OCCAMS) incorporating International Cancer Genome Consortium (ICGC)

Oesophageal and junctional adenocarcinomas (OAC) have a poor prognosis and the standard of care is cytotoxic chemotherapy with or without radiotherapy followed by surgery. In contrast to other cancers, as yet knowledge of the molecular pathogenesis of the disease has not been used to determine prognosis and therapy.

The OCCAMS (Oesophageal Cancer Clinical and Molecular Stratification) study is a network of clinical centres recruiting OAC patients for tissue collection. OAC patient data and tissue samples are used to attempt to identify clinical, demographic and molecular factors affecting disease progression. 

 

The aims of the OCCAMS study are to:

  • Better characterise the clinico-demographic risk factors
  • Characterise the molecular genetic landscape (DNA, RNA, epigenome)
  • Determine disease sub-types and develop new clinically relevant classification systems
  • Develop and validate improved clinical staging and prognostic algorithms
  • Ascertain new therapeutic targets for clinical trials

 

The OCCAMS project is recruiting – contact Nicola Grehan (Email:nsg25@mrc-cu.cam.ac.uk) for more information.

Current project status

 

Information for study participants regarding how we use person identifiable data can be found here 

 

Tissue collection and preparation

Any hospital that is a specialist centre for oesophago-gastric cancer is eligible to join the OCCAMS consortium.

Patients are recruited at the time of diagnosis and samples taken at times of clinically indicated interventions. The clinicians collecting the sample provide clinical and demographic information and frozen tumour material for one or more time points. Collection of blood provides a genomic reference and a potential resource to look for biomarkers present in the blood.

In addition to tumour and blood, lymph node and Barrett's tissue may be collected where appropriate.

Depending on sample type, samples are embedded in paraffin or frozen. Samples are transported to Cambridge for further processing and analysis.

A pathologist reviews the samples to confirm diagnosis and tumour cellularity. To be eligable for analysis, samples must be a minimum of 70% tumour cells. DNA and RNA are extracted using a strict QC process. DNA and RNA samples that meet required standards are used for DNA sequencing, PCR and gene expression arrays.

DNA samples are sent to Illumina in California for DNA sequencing. Sequence information is then made available to Simon Tavare's bioinformatics group at the Cambridge Institute.

 

Bioinformatics

Bioinformatics is performed by Simon Tavare's group at the University of Cambridge CRUK Cambridge Institute (CI).

An analysis pipeline, running on the CI's High Performance Computer Cluster (HPC), performs whole-genome analysis on the tumour and matched normal genomes.

The bulk of the analysis pipeline is concerned with identifying sequence variations between tumour and normal samples. A variety of software is employed to call inserts, deletions, loss of hetrozygosity and structural variations.

Statistical analysis is performed to identify potential driver genes and common processes in cancer progression.

The Tavare group works closely with the Fitzgerald group to investigate aspects such as genomic effects of chemotherapy, microbial genome contamination and genetic changes associated with lymph-node metatastisis and barrett's oesophagus.

As a part of the ICGC, sequence and expression data is submitted to the DCC for download by other collaborators.

 

Read more about ICGC and bioinformatics for this project.

 

Participating Centres:

We are collaborating with a wide range of NHS trusts across the UK who support sample and data collection of the project as well as scientific input and review. 

 

Publications

Facilitating a culture of responsible and effective sharing of cancer genome data. Siu LL, Lawler M, Haussler D, Knoppers BM, Lewin J, Vis DJ, Liao RG, Andre F, Banks I, Barrett JC, Caldas C, Camargo AA, Fitzgerald RC, Mao M, Mattison JE, Pao W, Sellers WR, Sullivan P, Teh BT, Ward RL, ZenKlusen JC, Sawyers CL, Voest EE. Nat Med. 2016 May 5;22(5):464-71. 

Whole-genome sequencing provides new insights into the clonal architecture of Barrett's esophagus and esophageal adenocarcinoma. Ross-Innes CS, Becq J, Warren A, Cheetham RK, Northen H, O'Donovan M, Malhotra S, di Pietro M, Ivakhno S, He M, Weaver JM, Lynch AG, Kingsbury Z, Ross M, Humphray S, Bentley D, Fitzgerald RC; Oesophageal Cancer Clinical and Molecular Stratification (OCCAMS) Study Group; Oesophageal Cancer Clinical and Molecular Stratification OCCAMS Study Group. Nat Genet. 2015 Sep;47(9):1038-46. doi: 10.1038/ng.3357. Epub 2015 Jul 20.

Mobile element insertions are frequent in oesophageal adenocarcinomas and can mislead paired-end sequencing analysis. Paterson AL, Weaver JM, Eldridge MD, Tavaré S, Fitzgerald RC, Edwards PA; OCCAMsConsortium. BMC Genomics. 2015 Jul 10;16:473. doi: 10.1186/s12864-015-1685-z.

Ordering of mutations in preinvasive disease stages of esophageal carcinogenesis. Weaver JM, Ross-Innes CS, Shannon N, Lynch AG, Forshew T, Barbera M, Murtaza M, Ong CA, Lao-Sirieix P, Dunning MJ, Smith L, Smith ML, Anderson CL, Carvalho B, O'Donovan M, Underwood TJ, May AP, Grehan N, Hardwick R, Davies J, Oloumi A, Aparicio S, Caldas C, Eldridge MD, Edwards PA, Rosenfeld N, Tavaré S, Fitzgerald RC; OCCAMS Consortium. Nat Genet. 2014 Aug;46(8):837-43. doi: 10.1038/ng.3013. Epub 2014 Jun 22.

A 4-gene signature predicts survival of patients with resected adenocarcinoma of the esophagus, junction, and gastric cardia. Peters CJ, Rees JR, Hardwick RH, Hardwick JS, Vowler SL, Ong CA, Zhang C, Save V, O'Donovan M, Rassl D, Alderson D, Caldas C, Fitzgerald RC; Oesophageal Cancer Clinical and Molecular Stratification (OCCAMS) Study Group. Gastroenterology. 2010 Dec;139(6):1995-2004.e15. doi: 10.1053/j.gastro.2010.05.080. Epub 2010 Jun 2.