1. Introduction and Survey Results
Dr Katie Snape,
Consultant Cancer Geneticist
UKCGG and St George’s University Hospitals NHS Foundation Trust

2. Background Increasing use of somatic testing in cancer tissue
Use of both somatic panels and WGS (with paired germline) in test directory
Increasing number of referrals into clinical genetics on basis of somatic data wondering if variants could be present in the germline
Increasing number of private and DTC referrals into clinical genetics

3. Current Situation No clear guidance on
Who is/should be eligible for referral to clinical genetics on the basis of a somatic test
What the likelihood of finding a germline variant is for an identified somatic variant
In associated tumour types
In non associated tumour types
How consent should operate for somatic testing where germline information may be identified
How these novel pathways will impact on resourcing in clinical genetics

4. Aims of today’s workshop
Review novel data which gives insight into the likelihood of a somatically identified variant also being present in the germline
Understand current and future policy on somatic/germline cancer gene testing from NHSE
Obtain consensus (as much as possible!) on what/who should and should not be referred from oncology to clinical genetics for further assessment/testing
Define/debate the novel clinical referral pathways which need to be implemented including where and how consent for germline testing should be undertaken
Present our outcomes as an expert working group of clinical scientists, oncologists, pathologists, clinical geneticists and genetic counsellors

5. Survey Responses 23 respondents
Multiple s saying people did not feel they have enough expertise to complete the survey so were non responders
At least two respondents stated they didn’t feel they knew enough to answer specific questions
Conclusion: difficult and complex area, with limited expertise amongst oncologists and geneticists

7. Take home messages Divided on whether the following should be included
Age cut offs for tumour types
No established germline association with cancer type
Variant allele frequency of 40%

8. Take home messages Divided on whether the following should be included
Age cut offs for tumour types
No established germline association with cancer type
Variant allele frequency of 40%

9. Take home messages Full or almost full agreement to include
Variant is in gene(s) for which diagnostic germline testing is available
Established germline association with cancer type
Variant is class 4/5 by clinical consensus (e.g. C-VIG), ≥ 2* on Clinvar or LoF variant where that is known pathogenic mechanism of gene

10. Comments on additional inclusion criteria
Assimilate alongside other molecular/pathological data (e.g. IHC/mutational signatures)
Clinical actionability e.g. Lower threshold for testing if affects clinical trial eligibility and higher threshold if no clear change in clinical management for patient/relatives
Likelihood of germline mutation being present if identified somatically

11. Genes in breast cancer
Other: PTEN/STK11/CHEK2/ATM/CDH1 (lobular)

12. Genes in serous ovarian cancer
Other: RAD51C, RAD51D, BRIP1

13. Genes in non-serous ovarian cancer
Other: RAD51C, RAD51D, BRIP1

14. Genes in colorectal cancer
Other: polyp panel genes

15. Genes in lung cancer

16. Themes of gene eligibility
Preference for known CPGs in associated tumour types
Multiple suggestions to include all CPGs for associated tumours
But significant proportion suggesting CPGs in non associated tumour types
Opting out of some tumour types which people felt less comfortable with

17. ?Age cut off

18. Comments on age cut off Tumour dependent
E.g. Different age cut offs for breast and prostate cancer with BRCA
Becomes complicated...
Age not only factor – also family history, histology etc.

19. Referrals

20. Referrals

21. Referrals

22. Referrals
Vast majority currently managing on case by case basis as small numbers
Would be helpful to have agreed national standardised criteria for accepting/rejecting referrals for testing or further assessment

23. Other comments Haem-onc samples – saliva?
Paired germline-somatic testing upfront would help resolve many of these issues
Need funding/staff/resources as well as clinical pathways
What is currently deliverable?
What extra resources do we need to implement these workflows?

24. Aims of today’s workshop
Review novel data which gives insight into the likelihood of a somatically identified variant also being present in the germline
Understand current and future policy on somatic/germline cancer gene testing from NHSE
Obtain consensus (as much as possible!) on what/who should and should not be referred from oncology to clinical genetics for further assessment/testing
Define/debate the novel clinical referral pathways which need to be implemented including where and how consent for germline testing should be undertaken
Present our outcomes as an expert working group of clinical scientists, oncologists, pathologists, clinical geneticists and genetic counsellors