ABSTRACT
53BP1 plays a crucial role in regulating DNA damage repair pathway choice and checkpoint signaling in somatic cells; however, its role in meiosis has remained enigmatic. In this study, we demonstrate that the Caenorhabditis elegans ortholog of 53BP1, HSR-9, associates with chromatin in both proliferating and meiotic germ cells. Notably, HSR-9 is enriched on the X chromosome pair in pachytene oogenic germ cells. HSR-9 is also present at kinetochores during both mitotic and meiotic divisions but does not appear to be essential for monitoring microtubule-kinetochore attachments or tension. Using cytological markers of different steps in recombinational repair, we found that HSR-9 influences the processing of a subset of meiotic double strand breaks into COSA-1-marked crossovers. Additionally, HSR-9 plays a role in meiotic X chromosome segregation under conditions where X chromosomes fail to pair, synapse, and recombine. Together, these results highlight that chromatin-associated HSR-9 has both conserved and unique functions in the regulation of meiotic chromosome behavior.
ABSTRACT
53BP1 plays a crucial role in regulating DNA damage repair pathway choice and checkpoint signaling in somatic cells; however, its role in meiosis has remained enigmatic. In this study, we demonstrate that the Caenorhabditis elegans ortholog of 53BP1, HSR-9, associates with chromatin in both proliferating and meiotic germ cells. Notably, HSR-9 is enriched on the X chromosome pair in pachytene oogenic germ cells. HSR-9 is also present at kinetochores during both mitotic and meiotic divisions but does not appear to be essential for monitoring microtubule-kinetochore attachments or tension. Using cytological markers of different steps in recombinational repair, we found that HSR-9 influences the processing of a subset of meiotic double strand breaks into COSA-1-marked crossovers. Additionally, HSR-9 plays a role in meiotic X chromosome segregation under conditions where X chromosomes fail to pair, synapse, and recombine. Together, these results highlight that chromatin-associated HSR-9 has both conserved and unique functions in the regulation of meiotic chromosome behavior.
ABSTRACT
INTRODUCTION: Incidence of peritoneal carcinomatosis (PC) after curative resection of stage II and III colon cancer varies widely. Although certain features are considered high risk for PC, the impact of these features on PC incidence is unclear. METHODS: A retrospective analysis was performed on patients ≥ 18 years old with resected stage II and III colonic adenocarcinoma treated at two academic institutions from 2007 to 2018. Clinicopathologic features, treatment and outcomes data were recorded. Patients with reported high-risk features (pT3N0-2 with mucinous/signet ring components, pT4, pN1c, perforation) were identified. The remaining stage II and III patients were used for comparison. RESULTS: Of 219 eligible patients, 93/219 (42.5%) were stage II and 126/219 (57.5%) were stage III. Median follow-up time was 25 (1-146) months. Adjuvant systemic treatment was administered to 133/219 (60.7%) patients. Overall incidence of PC was 14/219 (6.4%) and the median time to PC was 18 (1-37) months. The high-risk and comparison groups contained 113 and 106 patients, respectively. Incidence of PC was significantly different between groups (high-risk 9.7% vs comparison 2.8%, p = 0.04). Median time to PC was not significantly different between the groups [high-risk 17 (1-37) months vs comparison 20 (7-36) months, p = 0.88]. CONCLUSION: Overall PC incidence in patients with resected stage II and III colon cancer was 6.4%. Although the high-risk group developed PC at a significantly higher rate, the rate of PC in this group was still below 10%. The results of this study represent real-world rates of PC and should be taken into account when designing future studies.
