South London Genomic Medicine Centre Cancer Cases Dr Alison May Berner ST4 Academic Clinical Fellow in Medical Oncology 4th June 2018

Lung Case – 73 year old female Ct confirmed as only sight of disease

Lung Case – 73 year old female CT guided lung biopsy Lung adenocarcinoma Wild-type EGFR and ALK PDL1 3% Sample sent for 100K Resection of brain metastasis Radiotherapy to tumour bed Right lower lobe resection pT3pN2M1b For adjuvant therapy under oncology

Lung Case – 73 year old female 100K fresh frozen sample Two tier 1 variants in EGFR gene c.2504A>T (H835L) c.2497T>G (L833V) Literature search Previous case report of patient with same dual mutation DIRECT database Two cases of H835L + L833V 1 documented response to Gefitinib Three cases of L858R + L833V Possible to offer anti-EGFR therapy in metastatic setting Need to validate mutation DIRECT database: DNA-mutation inventory to refine and enhance cancer treatment (EGFR L833V, H835L; accessed 5-16-2018), http://www.mycancergenome.org/about/direct.

Breast Case – 36 year old female Self-detected left breast lump Mother also had breast cancer aged 37

Breast Case – 36 year old female Biopsy Grade 2 invasive ductal carcinoma ER 0, PR 0, HER2 negative 100K fresh frozen sample sent Neoadjuvant chemotherapy Anthracycline and Taxane Moderate response Negative BRCA test Left mastectomy and a sentinel node biopsy 

Breast Case – 36 year old female No actionable tier 1 variants Signature 3 identified Compatible with defect in homologous recombination pathway Loss of heterozygosity at BRCA1 locus Management as BRCA? Prophylactic surgery/screening Treatment if recurs

Colorectal Case – 67 year old male Positive faecal occult blood test Referred for flexible sigmoidoscopy Difficult CT colon Tumour at hepatic flexure PET CT Confirmed isolated tumour

Colorectal Case – 67 year old male Right Hemicolectomy Moderately to poorly differentiated adenocarcinoma Dukes B EMVI negative 0/22 lymph nodes involved Mismatch IHC abnormal - MLH1 and PMS2 absent Molecular analysis BRAF V600E mutation detected KRAS and NRAS no mutation No family history of colorectal cancer No adjuvant chemotherapy on balance of risk

Colorectal Case – 67 year old male 33 coding SNVs per megabase

Colorectal Case – 67 year old male Management of follow-up BRAF-directed trials if recurs Consider Immunotherapy if recurs

St George’s 100K Cancer Team Nirupa Murugaesu Ruth Pettegal Katie Snape Helen Hanson John Short George Morrissey Tracy Odigie Alison Berner Glen Brice Mary Brice Uzma Khan Iulia Munteanu Rahul Kurup Keith Rogerson