1. Mary Alikian ICHT Cancer validation update
WLGMC
Mary Alikian
ICHT
Cancer validation update

2. 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

3. 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

4. #Renal_case_Result_x1
male
Age 76
Gel IDs:
Diagnosis: Renal Cell carcinoma
CS /11/2016
Nephrectomy resection
Grade 1 clear cell renal cell carcinoma
pT1a N0 R0
CS /12/2017
left supraclavicular lymph node biopsy
Type II papillary renal cell carcinoma
pT3aN2 R0
Metastatic to hilar nodes and adrenal gland
CS /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

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

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

7. 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)

8. #Renal_case_Result_x2
male
Age 63
Gel IDs:
Diagnosis: Bladder
CS /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

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

10. Domain 1

11. Domain 2

12. 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.

13. 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