Guidelines for cytogenetic investigations in tumours

European Journal of Human Genetics (2016) 24, 6–13 & 2016 Macmillan Publishers Limited All rights reserved 1018-4813/16 www.nature.com/ejhg POLICY Guidelines for cytogenetic investigations in tumours Rosalind J Hastings1, Nick Bown2, Maria G Tibiletti3, Maria Debiec-Rychter4, Roberta Vanni5, Blanca Espinet6, Nadine van Roy7, Paul Roberts8, Eva van den Berg-de-Ruiter9, Alain Bernheim10, Jacqueline Schoumans11, Steve Chatters12, Zuzana Zemanova13, Marian Stevens-Kroef14, Annet Simons14, Sverre Heim15, Marta Salido6, Bauke Ylstra16 and David R Betts*,17 European Journal of Human Genetics (2016) 24, 6–13; doi:10.1038/ejhg.2015.35; published online 25 March 2015 Cytogenetic and molecular genetic data are of paramount importance in the diagnosis, prognosis, and risk stratification of patients with malignant diseases. Sometimes they even directly guide the choice of therapy.1 Disease-specific abnormalities, particularly translocations, can provide essential information to assist the Pathologist and/or Oncologist in assigning a diagnosis. In several diseases, tumour genetics correlate strongly with clinical risk; thus, cytogenetic information may help the Oncologist counsel the patient, choose a specific treatment, and/or modulate treatment intensity. Clinical trials may involve cytogenetic classification of patients to the appropriate treatment regimens. Currently, the provision of specific assays for acquired neoplasiaspecific genomic changes varies among and within countries as a range of laboratories offer diagnostic solid tumour genetics; these may include Cytogenetic, Pathology, Haematology, and Molecular Genetics laboratories. Technical standards and general guidelines for the analysis and the report of results on most solid tumours are lacking. To address these deficits, a tumour best practice meeting with invited tumour experts without conflict of interest was held on 23rd April 2013 in Oxford, United Kingdom. The aim was to produce professional guidelines for tumour genetic laboratories and to incorporate the standards imposed by generic European guidelines,2 regulatory bodies (ISO15189, 2012 Medical laboratories – requirements for quality and competence),3 reporting guidelines,4 ISCN,5 and acquired best practice guidelines, while taking into account the current practice in Europe. The guidelines are aimed principally at giving guidance on the minimum, standard cytogenetic analyses, which are applicable to different types of laboratories operating under different regulatory arrangements and are relevant if more specific recommendations are not available. It was universally acknowledged that information on ancillary techniques in use in most cytogenetic laboratories (eg, RT- PCR) or advanced techniques not always extensively performed in all laboratories (eg, next-generation sequencing (NGS)) were considered. The process for developing these evidence-based consensus guidelines included agreement on the need of general uniform rules on solid tumour analysis and reporting, discussion on the architecture of the guidelines, working group formation with different tasks (collection, analysis and comparison of any existing guidelines on this subject, type of tumours to be included according to published data and database consultation, method of analysis to be included, report formulation), circulation of the working group activities, formulation and circulation of the initial recommendations, draft and discussion, final consensus, and approval. It is noted that some elements of the tumour diagnostic service not subject to statute may be varied according to local constraints and agreements. Therefore, these guidelines are minimum requirements and additional professional judgment may be of paramount importance under many circumstances. In addition, as new techniques, particularly NGS, as well as clinical evidence, are becoming available all the time, these should be kept under constant review. Notes: The use of ‘must’ in this document indicates a requirement and the use of ‘should’ indicates a recommendation. Where there appears to be contradiction between available guidelines, the most recently published ones should be taken to apply to all. All diagnostic laboratories should be accredited to national or internationally accepted standards (ISO15189).3,6 Laboratories should participate in an External Quality Assessment Scheme7 in all aspects of their service for which a scheme is available. LABORATORY STAFFING The laboratory must have either a head of laboratory or a senior staff member who is knowledgeable in the cytogenetic abnormalities, the appropriate test(s) required, and the clinical significance of results for 1 Women's Centre, John Radcliffe Hospital, Oxford University Hospitals NHS Trust, Oxford, UK; 2Northern Genetics Service, Institute of Genomic Medicine, Central Parkway, Newcastle, UK; 3UO Anatomia Patologica, Ospedale di Circolo-Polo Universitario, Varese, Italy; 4Laboratory for Genetics of Malignant Disorders, Department of Human Genetics, University Hospital Gasthuisberg, UZ Leuven, Leuven, Belgium; 5Department of Biomedical Sciences, University of Cagliari, Cittadella Universitaria, Monserrato, Italy; 6Laboratori de Citogenètica Molecular, Servei de Patologia, Hospital del Mar, Barcelona, Spain; 7Centre for Medical Genetics, University Hospital Ghent, Ghent, Belgium; 8Cytogenetics Department, St James’s Hospital, Leeds, UK; 9Department of Genetics, University of Groningen, University Medical Centre Groningen, RB Groningen, The Netherlands; 10 Génétique des tumeurs (INSERM U985), Laboratoire de Cytogénétique, Pathologie Moléculaire Gustave Roussy, Paris-Villejuif, France; 11Cancer Cytogenetic Unit, Lausanne University Hospital, CHUV, Lausanne, Switzerland; 12Haematology, Cellular and Molecular Diagnostic Service, Great Ormond St Hospital, London, UK; 13Center of Oncocytogenetics, Institute of Clinical Biochemistry and Laboratory Diagnostics, General University Hospital and First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic; 14Radboud University Nijmegen Medical Centre Department of Human Genetics, HB Nijmegen, The Netherlands; 15Institute for Cancer Genetics and Informatics, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway; 16Department of Pathology, Cancer Center Amsterdam, VU University Medical Center, MB Amsterdam, The Netherlands; 17Department of Clinical Genetics, Our Lady's Children's Hospital, Crumlin, Dublin, Ireland *Correspondence: DR Betts, Department of Clinical Genetics, Our Lady's Children's Hospital, Crumlin, Dublin 12, Ireland. Tel: +353 1 4096738; Fax: +353 1 4096971; E-mail: Received 6 June 2014; revised 19 January 2015; accepted 3 February 2015; published online 25 March 2015 Tumour cytogenetic guidelines RJ Hastings et al 7 all tumour types that the laboratory may process. Appropriately trained staff members analysing these tumours should be familiar with the reason for the test and findings t (...truncated)