Distant metastasis is one of the leading causes of lung cancer death. Detecting the early-stage molecular alternations in primary tumors, such as gene expression differences, provides a ''prognostic'' value to the precaution of tumor metastasis. The aim of this article is to screen and identify the metastasis-related genes in human squamous cell lung carcinoma. Primary tumor tissues of nine patients with subsequent metastasis and eight patients without metastasis were selected to perform the gene microarray experiment. GO and pathway analyses were used to determine the differentially expressed genes. Two identified genes were further validated by real-time quantitative reverse transcription polymerase chain reaction (PCR) (real-time qRT-PCR). Two hundred and thirty-eight differentially expressed genes were detected in gene chip experiment, including 51 up-regulated genes and 187 down-regulated genes. These genes were involved in several cellular processes, including cell adhesion, cell cycle regulation, and apoptosis. GO analysis showed that the differentially expressed genes participated in a wide ranging of metastasis-related processes, including extracellular region and regulation of liquid surface tension. In addition, pathway analysis demonstrated that the differentially expressed genes were enriched in pathways related to cell cycle and Wnt signaling. Real-time qRT-PCR validation experiment of LCN2 and PDZK1IP1 showed a consistent up-regulation in the metastasis group. The metastasis of human squamous cell lung carcinoma is a complex process that is regulated by multiple gene alternations on the expression levels. The 238 differentially expressed genes identified in this study presumably contain a core set of genes involved in tumor metastasis. The real-time qRT-PCR results of PDZK1IP1 and LCN2 validated the reliability of this gene microarray experiment. Anat Rec,
Background: Li-Fraumeni syndrome (LFS) is a rare autosomal dominant inherited cancer syndrome; clinical diagnosis of it is mainly based on familial and personal history of cancer. Currently, most clinicians are lack of knowledge and experience of this rare disease, resulting in a difficulty to identify it. Consider that this is a rare tumor-type syndrome and 60-80% of the patients have germline variants of TP53, herein, we analyzed germline pathogenic/likely pathogenic (P/LP) TP53 variants in a Chinese tumor cohort with unknown familial history, and successfully established an analysis process to better screen for LFS patients. Methods: We retrospectively analyzed the germline TP53 mutations of a total of 19,226 Chinese tumor patients with unknown familial history. The screening process of LFS patients was as follows: 1) Germline P/LP TP53 variants must satisfy P/LP in any of the three databases: UMD_TP53, ClinVar or HGMD. It also must be defined as “non-functional” mutations in IARC database which includes all TP53 germline mutations of clinically determined LFS patients; 2) Follow up the familial and personal histories of patients with germline P/LP TP53 variants. Results: After screening, 26 germline P/LP TP53 variants were obtained, which involved 54 patients, mainly in brain cancer (34 pts) and lung cancer (9 pts). The median age of these 34 brain cancer patients was younger than that of 5,845 brain cancer patients in the cohort (28 vs. 44 year-old). Yet no such phenomenon was observed in lung cancer. It is necessary for young brain cancer patients to detect germline TP53 mutations. We then analyzed the relationship between germline P/LP TP53 variants and LFS in the 54 patients. According to the Chompret criterion of LFS, two patients who respectively had adrenocortical carcinoma (R175H of TP53) and choroid plexus carcinoma (G245S) were both LFS patients regardless of whether they had a familial history. We finally obtained follow-up information of 17 patients. Among them, four brain cancer patients (R248Q/R158H/C238Y/M237I), one lung cancer patient (R175H) and one leiomyosarcoma patient (R213Q) had family members who had cancers before 46-year-old. Another brain cancer patient (G245S; 1/17) had more than one cancer before 46-years-old. Hence, these seven patients (7/17; 41.18%) were also defined as LFS patients by the Chompret criterion. In total, 9 patients had LFS. It shows a high positive detection rate in our cohort by our analysis process. Conclusions: We have established an analysis process based on germline P/LP TP53 variants, which can efficiently screen for LFS patients in clinic. Citation Format: Changyu Lu, Yu Fang, Fachen Zhou, Yuntong Liu, Hongchuan Niu, Kai Li, Tonghui Ma, Xiaoyan Zhang. Enrichment and screening of LFS patients by analyzing TP53 germline mutations of a Chinese cancer cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 810.
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