Background. Tumor multigene next-generation sequencing (NGS) is increasingly being offered to cancer patients to guide clinical management and determine eligibility for clinical trials. We undertook a review of studies examining the knowledge and attitudes of patients and oncologists regarding the primary results and potential secondary findings of such testing. Materials and Methods. A search was conducted through the MEDLINE database using the following keywords: "neoplasms" and "molecular sequencing / genome sequencing / tumor profiling / NGS / whole exome sequencing" and "patient / oncologist" and "knowledge / attitudes / satisfaction / experience / evaluation / perspective / practice / preference." Articles meeting the inclusion criteria and additional relevant articles from their references were selected. Results. From 1,142 publications identified by the search and 9 from references, 21 publications were included in the final review. Patients generally had positive attitudes

No abstract

Genetic lesions are central contributors to cancer development and progression, and understanding the sources of these lesions will provide a better understanding of the mechanisms of carcinogenesis. Our previous work showed that the uncharacterized murine Fam72a gene promotes mutagenic DNA repair during antibody maturation by causing the degradation of Uracil DNA glycosylase 2 (UNG2), a component of the base excision repair (BER) system. Humans encode four almost identical paralogues of FAM72 called FAM72A-D, which are absent in all other mammalian genomes, including those of non-human primates. The role of these four paralogues in human biology is unknown. Intriguingly, a previous report showed that FAM72A is over-expressed in many cancers. Since FAM72A promotes mutagenesis by degradation of UNG2, we hypothesized that overexpression of the FAM72 gene family might promote cancer development and progression. Here we show that FAM72A-D is overexpressed in many human cancers and inversely correlates with UNG2 protein levels in tumorigenic tissue. However, FAM72A but not FAM72B-D causes degradation of UNG2. Consistent with this effect, FAM72 expression correlates with a higher mutation load in many tumor types. Since genetic mutations are associated with cancer development and progression, we tested whether FAM72 expression is associated with disease outcomes. Indeed, we found that high FAM72 expression was associated with poorer survival in several cancers. To directly test if Fam72a is sufficient to promote cancer, we generated transgenic mice that overexpress Fam72a in multiple tissues. We observed that Fam72a overexpression promotes increased colonic polyps in the Apcmin background compared to controls. These data show that the novel FAM72 gene family are drivers of cancer development in both mice and humans and advances our understanding of the underlying molecular mechanisms that precipitate cancer development and progression. This work is supported by a grant from the CIHR (PJT-180269). Citation Format: Yuqing Feng, Bhupesh Thakur, Jeffery Bruce, Sami Mamand, Melika Shirdarreh, Matthew Wong, Jennifer Silvester, Ming Han, Mohammad Kashem, Amin Zia, David Cescon, Tervor Pugh, Rossanna C. Pezo, Alberto Martin. The FAM72 gene family promotes cancer development by disabling the base excision repair system [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1217.

Introduction: To date, the ketogenic diet (KD) has been shown to improve certain health conditions such as seizure. These positive effects have been partly mediated through the gut microbiome. However, research on KD's impact on colorectal cancer (CRC) and the gut microbiome of cancer patients that use KD has been scant. This study aims to investigate the role of KD in the co-evolution of gut microbial composition and CRC progression. We hypothesize that KD alters overall species diversity through either elimination of harmful bacterial genera or perpetuation of beneficial gut microbiota which could ultimately be the mechanism underlying positive CRC outcomes. Methods: In order to test this hypothesis, we propose a murine study using Apc Min/+ (multiple intestinal neoplasia) CRC mouse models in C57BL/6J background. The mice will either be given normal chow (control group) or KD (87% fat) for 8 weeks. Mice will be euthanized at the end of the experiment and analyzed in terms of polyp size and polyp number in the small intestine and colon. Frozen colon tissue will also be used to extract mRNA for quantitative polymerase chain reaction (qPCR) analysis of TH17 cytokine production. Gut microbiome composition will be analyzed by sequencing of 16S rRNA genes. To compare microbiome structure between diet groups, alpha diversity will be used to measure the differences in gut microbial structure in the control and experimental groups. Results: We would expect that mice fed a KD would have altered microbiota diversity, a decreased level of cytokine production, as well as fewer and smaller polyps (as measured in the small intestine and colon). Discussion: Analysis of the gut microbiota post-treatment, in conjunction with assessment of cytokine levels will help to set correlations between microbial gut activity and CRC progression. Conclusion:The results of this experiment could give insight into the impact of KD on development and progression of CRC; which could be used to develop therapeutic or dietary interventions.