Mary Alikian ICHT Cancer validation update WLGMC Mary Alikian ICHT Cancer validation update

Map of GMCs New ICHT RMH RBH and WEH C&W North-West London Mental health NHS Trust (Dementia and Obesity) New ICHT RMH RBH and WEH C&W

WLGMC cancer results - August 2018 2017 2018 (as of 16/08) Results Received 85 73 Discussed at Tumour Sequencing Board 2 Validated 1 - Reported/referred to disease specific MDT

#Renal_case_Result_x1 male Age 76 Gel IDs: 220000096 Diagnosis: Renal Cell carcinoma CS16-21964 30/11/2016 Nephrectomy resection Grade 1 clear cell renal cell carcinoma pT1a N0 R0 CS17-23716 20/12/2017 left supraclavicular lymph node biopsy Type II papillary renal cell carcinoma pT3aN2 R0 Metastatic to hilar nodes and adrenal gland CS18-7268 20/04/2018 Left neck dissection metastatic solid/papillary renal cell carcinoma Clinical management Surgery – radical nephrectomy Maintenance therapy Clinical conclusion The patient was diagnosed with Grade 1 clear cell renal cell carcinoma and metastatic Type II papillary renal cell carcinoma, present in left adrenal gland and hilar lymph nodes. Patient developed post-surgical acute gangrenous cholecystitis. Subsequent biopsy of left supraclavicular lymph node showed metastatic papillary renal cell carcinoma. Discussed at 2 GTABs: 28/03/2018 15/08/2018 Note Extracted DNA sent from FF tissue stored from Nephrectomy specimen. morphology displays clear cell renal cell carcinoma (ccRCC) features. The microscopic investigation describes two distinct tumours: Grade 1 clear cell renal cell carcinoma Type II papillary renal cell carcinoma

Case HH-3 Total number of SNVs 23,330 Total Somatic InDels 25,496 Total Somatic SVs 206 1 3 16 25 9 other

Domain 1 There were no domain 1 variants reported. Domain 2

Copy number variants (CNVs) CNV loss at 3q does not include VHL, FHIT, SETD1 and BAP1 Conclusion: No evidence of hyper-mutation No evidence of tumour being caused by lynch syndrome No actionable variants identified. No domain 1 variants were identified. Some of the Domain 2 variants are known to be associated with ccRCC. Validate in clinical context should the patient relapse. Could do Submit to Gel DNA extracted from the papillary tumour if tissue is available (FF vs FFPE)

#Renal_case_Result_x2 male Age 63 Gel IDs: 220000072 Diagnosis: Bladder CS16-15277 23/8/2016 Cystoprostatectomy Urothelial carcinoma High grade urothelial carcinoma with squamous differentiation pT2 N0 R0 prostate adenocarcinoma Gleason 3+4=7 pT2c N0 R0 Clinical management Surgery – prostatectomy and cystectomy Maintenance therapy Discussed at 2 GTABs: 28/03/2018 15/08/2018 Clinical conclusion Not much clinical information is available. The patients was diagnosed with High grade urothelial carcinoma with squamous differentiation plus prostate adenocarcinoma. Undergone Cystoprostatectomy and currently under survailance. Note Extracted DNA sent from FF tissue stored from bladder tumour. The microscopic investigation describes two distinct tumours: Grade 1 clear cell renal cell carcinoma Type II papillary renal cell carcinoma

Case HH-3 Total number of SNVs 160,961 Total Somatic InDels 256,748 Total Somatic SVs 118 1 3 16

Domain 1

Domain 2

Copy number variants (CNVs) CNV loss at 3q does not include VHL, FHIT, SETD1 and BAP1 Other CNV loses reported in chr1, 7, 9, 10, 11, 12, 14, 15, 16, 17, 19, 20, 22 CNV gains reported in chr1 and 3 VHLL CNV x5 No SETD2 CNV Conclusion: evidence of hyper-mutation which could be the driver for the tumour development. Large number of domain 2 variants might be consistent with microsatellite instability. No germline findings were reported. The patient may benefit from clinical genetic appointment if there is a family history consistent with Lynch syndrome.

Acknowledgements Julian Readhead Teena Furgason Sanjay Popat Graham Rose Priya Yoganathan Genomics nurses James Wingfield Naresh Kikkeri Andrew Smith Jamshid Khorashad Gerry Thomas IMPL staff GMC staff Tissue bank Staff RMH Mol Diagnostics lab staff