Haematological Malignancies Update Cancer V&R work shop 04/06/18 Dr Shirley Henderson

Haematological malignancies – creating new clinical pathways for WGS Although there is a long track record of the genetic analysis of both liquid and solid haematological tumours to aid diagnosis and therapy choice, significant clinical pathway adaptions are required to provide appropriate material for WGS. For solid haematological tumours (e.g lymphoma) the challenges are similar to other solid tumours i.e requirement for fresh frozen samples to obtain optimal WGS. For liquid haematological cancers where it is usually possible to obtain good quality (unfixed) tumour DNA from blood or bone marrow, the challenge lies with the collection of suitable samples for germline DNA.

Alternative germlines for Haematological Malignancies Cultured Fibroblasts, Post treatment blood (taken once malignant cells have been cleared). Saliva Various options are being explored, all alternative germlines have pros and cons (e.g delays and/or tumour contamination) – work being carried out to ascertain which will give best results AND firt into clinical pathways. Reference Germ Line Sorted T cells Uncultured Skin Biopsy

Acute Myeloid Leukaemia Updated WHO classification of myeloid neoplasms and acute leukaemia (2016) * now 23 sub types of AML and related neoplasms Different sub types can require different therapy and will have different prognoses Multiple molecular tests (for small & structural variants) may be needed to properly classify into appropriate sub groups WGS has the potential to identify all types of molecular variants Potential benefit of WGS in AML *

Haematological Malignancies Time Line (main programme)

Haematological Malignancies Recruitment (GMC self reported samples in process & and passed QC) as of 18nd May 2018

Haematological Malignancies – Genomics England Data GMC # Participants registered # Samples sent # Samples at UKB # Samples at Illumina # Sequence returned East of England 26 South London 19 18 6 4 Greater Manchester 34 12 North East and Cumbria 14 North Thames 100 46 Oxford 47 81 54 Wessex 23 20 10 West Midlands 2 West of England Total 323 203 82 38

Next Haem Onc WEBEX July 3rd 2-3:30pm