Somatic cancer genetics in the UK: real-world data from phase I of the Cancer Research UK Stratified Medicine Programme

Abstract

IntroductionPhase I of the Cancer Research UK Stratified Medicine Programme (SMP1) was designed to roll out molecular pathology testing nationwide at the point of cancer diagnosis, as well as facilitate an infrastructure where surplus cancer tissue could be used for research. It offered a non-trial setting to examine common UK cancer genetics in a real-world context.MethodsA total of 26 sites in England, Wales and Scotland, recruited samples from 7814 patients for genetic examination between 2011 and 2013. Tumour types involved were breast, colorectal, lung, prostate, ovarian cancer and malignant melanoma. Centralised molecular testing of surplus material from resections or biopsies of primary/metastatic tissue was performed, with samples examined for 3–5 genetic alterations deemed to be of key interest in site-specific cancers by the National Cancer Research Institute Clinical Study groups.Results10 754 patients (98% of those approached) consented to participate, from which 7814 tumour samples were genetically analysed. In total, 53% had at least one genetic aberration detected. From 1885 patients with lung cancer, KRAS mutation was noted to be highly prevalent in adenocarcinoma (37%). In breast cancer (1873 patients), there was a striking contrast in TP53 mutation incidence between patients with ductal cancer (27.3%) and lobular cancer (3.4%). Vast inter-tumour heterogeneity of colorectal cancer (1550 patients) was observed, including myriad double and triple combinations of genetic aberrations. Significant losses of important clinical information included smoking status in lung cancer and loss of distinction between low-grade and high-grade serous ovarian cancers.ConclusionNationwide molecular pathology testing in a non-trial setting is feasible. The experience with SMP1 has been used to inform ongoing CRUK flagship programmes such as the CRUK National Lung MATRIX trial and TRACERx.

Sperm protein 17 targeting for epithelial ovarian cancer treatment in the era of modern immunoengineering

“…Examples of these antigens are shown in Table 1 . 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 Most of these antigens arise due to either overexpression or aberrant expression of normal cellular proteins. Extracellular antigens include Sp17, 18 MUC1, 11 and mesothelin.…”

“… 14 Intracellular tumor antigens in ovarian cancer cells have also been demonstrated in various studies, including the MAGE family of antigens, 16 NY-ESO1, 17 and LACE-1. 17 Other antigens including neoantigens 24 , 25 , 26 , 27 may have arisen from random mutations associated with neoplastic process, although genomic analysis of EOC has found the tumor cells to harbor low mutational burden. 28 …”