Oncotarget | https://doi.org/10.18632/oncotarget.27061 Kazuo Asanoma, Emiko Hori, Sachiko Yoshida, Hiroshi Yagi, Ichiro Onoyama, Keisuke Kodama, Masafumi Yasunaga, Tatsuhiro Ohgami, Eisuke Kaneki, Kaoru Okugawa,...

Okazawa-Sakai M, et al. J Gynecol Oncol. 2024 Oct;36:e38. https://doi.org/10.3802/jgo.2025.36.e38

The functional single nucleotide polymorphism (SNP) in the MDM2 promoter region, SNP309, is known to be associated with various diseases, particularly cancer. Although many studies have been performed to demonstrate the mechanism of allele-specific expression (ASE) on SNP309, they have only utilized in vitro techniques. It is unknown whether ASE of MDM2 is ascribed solely to SNP309, in vivo. We attempted to evaluate ASE of MDM2 in vivo using post-labeling followed by automated capillary electrophoresis under single-strand conformation polymorphism conditions. For measuring a quantitative difference, we utilized the SNPs on the exons of MDM2 as markers, the status of which was heterozygous in a large population. To address the cause of ASE beyond 20 %, we confirmed sequences of both MDM2-3’UTR and promoter regions. We assessed the SNP which might be the cause of ASE using biomolecular interaction analysis and luciferase assay. ASE beyond 20 % was detected in endometrial cancers, but not in cancer-free endometria samples only when an SNP rs1690916 was used as a marker. We suspected that this ASE in endometrial cancer was caused by the sequence heterogeneity in the MDM2-P2 promoter, and found a new functional polymorphism, which we labelled SNP55. There was no difference between cancer-free endometria and endometrial cancer samples neither for SNP55 genotype frequencies nor allele frequencies, and so, SNP55 alone does not affect endometrial cancer risk. The SNP55 status affected the DNA binding affinity of transcription factor Sp1 and nuclear factor kappa-B (NFκB). Transcriptional activity of the P2 promoter containing SNP55C was suppressed by NFκB p50 homodimers, but that of SNP55T was not. Only ASE-positive endometrial cancer samples displayed nuclear localization of NFκB p50. Our findings suggest that both the SNP55 status and the NFκB p50 activity are important in the transcriptional regulation of MDM2 in endometrial cancers.

The rare phenomenon of tumor-to-tumor metastasis was first described in 1930. The donor neoplasm is most frequently lung or breast carcinoma, whereas intracranial meningiomas are reportedly the commonest recipient neoplasm. Here we report a case of metastasis from a primary gastric cancer to a uterine lipoleiomyoma. A 65-year-old woman presented with locally advanced gastric cancer with computed tomography (CT) evidence of peritoneal dissemination and a 9 cm pelvic mass. She underwent 16 courses of TS-1/cisplatin chemotherapy, which achieved significant tumor reduction. However, repeat CT and magnetic resonance imaging revealed a 9 cm diameter pelvic mass adjacent to the uterus. The mass was heterogeneously hyperintense on T1- and T2-weighted images with some low signal spots on fat-suppressed T1-weighted images, suggesting a benign ovarian tumor such as a mature cystic teratoma. After 3 months, pelvic CT revealed a 10 cm multilocular cystic mass that exhibited heterogeneous enhancement after intravenous contrast administration. A diagnostic laparotomy revealed a subserosal uterine tumor extending into the right broad ligament; total abdominal hysterectomy and bilateral salpingo-oophorectomy was performed. The uterine tumor showed histological features of lipoleiomyoma infiltrated by well- to moderately differentiated carcinoma cells that were similar to those of the gastric biopsy, supporting a diagnosis of metastatic gastric adenocarcinoma.