Cancer Genetics最新文献

{"title":"Machine learning analysis of CD4+ T cell gene expression in diverse diseases: insights from cancer, metabolic, respiratory, and digestive disorders.","authors":"HuiPing Liao, QingLan Ma, Lei Chen, Wei Guo, KaiYan Feng, YuSheng Bao, Yu Zhang, WenFeng Shen, Tao Huang, Yu-Dong Cai","doi":"10.1016/j.cancergen.2024.12.004","DOIUrl":"10.1016/j.cancergen.2024.12.004","url":null,"abstract":"<p><p>CD4⁺ T cells play a pivotal role in the immune system, particularly in adaptive immunity, by orchestrating and enhancing immune responses. CD4⁺ T cell-related immune responses exhibit diverse characteristics in different diseases. This study utilizes gene expression analysis of CD4⁺ T cells to classify and understand complex diseases. We analyzed the dataset consisting of samples from various diseases, including cancers, metabolic disorders, circulatory and respiratory diseases, and digestive ailments, as well as 53 healthy controls. Each sample contained expression data for 22,881 genes. Four feature ranking algorithms, incremental feature selection method, synthetic minority oversampling technique, and four classification algorithms were utilized to pinpoint essential genes, extract classification rules and build efficient classifiers. The following analysis focused on genes across rules, such as AK4, CALU, LINC01271, and RUSC1-AS1. AK4 and CALU show fluctuating levels in diseases like asthma, Crohn's disease, and breast cancer. The analysis results and existing research suggest that they may play a role in these diseases. LINC01271 generally has higher expression in conditions including asthma, Crohn's disease, and diabetes. RUSC1-AS1 is more expressed in chronic diseases like asthma and Crohn's, but less in acute illnesses like tonsillitis and influenza. This highlights the distinct roles of these genes in different diseases. Our approach highlights the potential for developing novel therapeutic strategies based on the transcriptional profiles of CD4⁺ T cells.</p>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"290-291 ","pages":"56-60"},"PeriodicalIF":1.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142899742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Screening and identification of gene expression in large cohorts of clinical tissue samples unveils the major involvement of EZH2 and SOX2 in lung cancer.","authors":"Niharika, Ankan Roy, Ratan Sadhukhan, Samir Kumar Patra","doi":"10.1016/j.cancergen.2024.11.006","DOIUrl":"10.1016/j.cancergen.2024.11.006","url":null,"abstract":"<p><p>Lung adenocarcinoma (LUAD), the primary subtype of Non-Small Cell Lung Cancer (NSCLC), accounts for 80 % to 85 % of cases. Due to suboptimal screening method, LUAD is often detected in late stage, leading to aggressive progression and poor outcomes. Therefore, early disease prognosis for the LUAD is high priority. In order to identify early detection biomarkers, we conducted a meta-analysis of mRNA expression TCGA and GTEx datasets from LUAD patients. A total of 795 differentially expressed genes (DEGs) were identified by exploring the Network-Analyst tool and utilizing combined effect size methods. DEGs refer to genes whose expression levels are significantly different (either higher or lower) compared to their normal baseline expression levels. KEGG pathway enrichment analysis highlighted the TNF signaling pathway as being prominently associated with these DEGs. Subsequently, using the MCODE and CytoHubba plugins in Cytoscape software, we filtered out the top 10 genes. Among these, SOX2 was the only gene exhibiting higher expression, while the others were downregulated. Consequently, our subsequent research focused on SOX2. Further transcription factor-gene network analysis revealed that enhancer of zeste homolog 2 (EZH2) is a significant partner of SOX2, potentially playing a crucial role in euchromatin-heterochromatin dynamics. Structure of SOX2 protein suggest that it is a non-druggable transcription factor, literature survey suggests the same. SOX2 is considered challenging to target directly, or \"non-druggable,\" because of several intrinsic properties that make it difficult to design effective therapeutic agents against it. The primary function of SOX2 is to bind DNA and regulates gene expression. Unlike enzymes or receptors with defined active sites or binding pockets, transcription factors typically have relatively flat or diffuse surfaces that do not offer obvious \"pockets\" for small molecules to bind effectively. Hence, we drove our focus to investigate on potential drug(s) targeting EZH2. Molecular docking analyses predicted most probable inhibitors of EZH2. We employed several predictive analysis tools and identified GSK343, as a promising inhibitor of EZH2.</p>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"290-291 ","pages":"16-35"},"PeriodicalIF":1.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142796365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic profile in primary tumor tissue of advanced lung adenocarcinoma patients with adrenal metastasis.","authors":"Haiqiao Pan, Hongbin Zhang, Yongqian Zhang, Xiaojing Chen, Zhai Liu, Yajing Wu, Na Bai, Yan Shi, Min Zhao, Lingling Zhu","doi":"10.1016/j.cancergen.2024.12.001","DOIUrl":"10.1016/j.cancergen.2024.12.001","url":null,"abstract":"<p><p>The aim of this study was to examine the genomic characteristics and explore the molecular mechanisms underlying adrenal metastases in lung adenocarcinoma. 57 patients diagnosed with lung adenocarcinoma (LUAD) and adrenal metastases (AM) were enrolled, alongside 33 controls diagnosed with non-adrenal metastases (non-AM) at the time of diagnosis. The primary lung cancer tissue sample were analyzed using next-generation sequencing. The molecular and clinical features were correlated with clinical outcomes. TP53, EGFR and KRAS were the most frequently mutated gene in both groups. EGFR mutations, especially rare variants (G724A, L747P, Q701 L, G719C, V769 L and S768I), exhibited significant enrichment in the non-AM group (P<0.001). An elevated age-related signature in the group of patients with AM, whereas the non-AM group exhibited a higher BRCA signature. Potential prognostic biomarkers such as KEAP1, LRP1B, NOTCH1 and RET mutations were detected in the non-AM group, while ALK mutations in the AM group correlated with shorter overall survival (P<0.001). KRAS mutations in the early synchronous adrenal metastases group were also associated with shorter OS (P<0.001). The analysis of 425 tumor genes in 29 patients with adrenal metastases showed significant enrichment in pathways associated with invasion and metastasis, including TNF signaling pathway and TGF-β signaling pathway. Patients without EGFR mutations in LUAD need to be more concerned about adrenal metastases. Meanwhile, patients with adrenal metastases harboring ALK or KRAS mutations have a poor prognosis and require more aggressive treatment. The TNF and TGF-β pathways might be associated with adrenal metastasis.</p>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"290-291 ","pages":"36-43"},"PeriodicalIF":1.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnostic and prognostic potential of FBXO8 expression in kidney renal clear cell carcinoma and its regulation of renal adenocarcinoma cells.","authors":"Zhouan Luo, Xiaoping Wu, Juanxia Xie, Hao Tang, Jingqi Chen, Dongcai Ye, Shangwen Dou, Songning Chen","doi":"10.1016/j.cancergen.2024.11.004","DOIUrl":"10.1016/j.cancergen.2024.11.004","url":null,"abstract":"<p><strong>Background: </strong>The F-box protein 8 Gene (FBXO8) has been shown to suppress invasion and metastasis in various cancer types. Recurrence and drug resistance pose significant challenges in renal cell carcinoma (RCC). Identifying novel biomarkers is crucial for addressing these issues.</p><p><strong>Methods: </strong>Data on RNA sequencing and patient survival for KIRC was obtained from The Cancer Genome Atlas (TCGA), UALCAN, and Gene Expression Omnibus (GEO) databases. We confirmed FBXO8 gene expression and its impact on survival. Clinical characteristics were classified, and FBXO8 expression differences among various categories were observed. We conducted biofunctional predictions and analyzed the tumor microenvironment (TME), immune cell infiltration, and immune checkpoints in relation to FBXO8 expression. FBXO8 was overexpressed using a plasmid, and we assessed Kidney renal clear cell carcinoma (KIRC) cell proliferation, migration, and apoptosis through CCK8, wound healing tests, and western blot analysis.</p><p><strong>Results: </strong>Our findings revealed decreased FBXO8 expression in KIRC, with patients exhibiting low FBXO8 expression experiencing shorter survival times. The low expression group showed elevated TME immune and estimate scores. Biofunctional analyses indicated that FBXO8 expression was notably linked to drug metabolism cytochrome P450, nutrition disease, receptor-ligand activity, and neuroactive ligand-receptor interaction. Furthermore, we discovered significant correlations between FBXO8 expression and immune cell infiltration, as well as checkpoints such as CD274. Overexpression (OE) of FBXO8 led to a marked reduction in cell proliferation and migration, along with increased apoptosis, as evidenced by apoptosis-related protein expression.</p><p><strong>Conclusion: </strong>This study demonstrates that FBXO8 serves as a biomarker for KIRC and plays a role in regulating cell proliferation, migration, and apoptosis.</p>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"290-291 ","pages":"6-15"},"PeriodicalIF":1.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142796361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microsatellite instability and high tumor mutational burden detected by next generation sequencing are concordant with loss of mismatch repair proteins by immunohistochemistry.","authors":"Richard K Yang, Hector Alvarez, Antony San Lucas, Sinchita Roy-Chowdhuri, Asif Rashid, Hui Chen, Leomar Y Ballester, Keith Sweeney, Mark J Routbort, Keyur P Patel, Rajyalakshmi Luthra, L Jeffrey Medeiros, Gokce A Toruner","doi":"10.1016/j.cancergen.2024.12.002","DOIUrl":"10.1016/j.cancergen.2024.12.002","url":null,"abstract":"<p><p>Impairment of DNA mismatch repair function in neoplasms can be assessed by DNA-based methods to assess for high microsatellite instability (MSI-High) or immunohistochemical (IHC) analysis to assess for deficiency of mismatch repair proteins (dMMR). Neoplasms with mismatch repair deficiency often have high tumor mutational burden (TMB-High). MSI-High, dMMR, and TMB-High are all histology agnostic biomarkers for potential therapy using immune checkpoint inhibitors (ICI). In this single center, retrospective study, our primary aim was to assess if NGS-based positive TMB/MSI findings are concordant with patient matched concurrent MMR IHC studies. In addition, we determined if positive TMB/MSI findings are attributable to genetic/epigenetic alterations of MMR genes. Finally, we explored potential associations between IHC, TMB and MSI findings and specific tumor types We screened 4,258 patients in our database who had tumor-normal-testing with our institutional high-throughput NGS-based CLIA assay between Apr 1, 2021-August 31, 2022 for TMB and MSI. We identified 65 patients who had neoplasms with documented TMB-High/MSI-High (n = 59) or TMB-High/MSI-Undetermined (n = 6) results as well as concurrent IHC results for MMR proteins [colorectal (n = 25), endometrial (n = 28), prostatic (n = 7), urothelial (n = 3), other (n = 5)]. The concordance between positive NGS TMB/MSI and MMR results was 98 %. Genetic/epigenetic alterations of MMR genes were documented in 78 % of the neoplasms. IHC studies for dMMR proteins revealed loss of MLH1/PMS2 (n = 33), MSH2/MSH6 (n = 14), MLH1/MSH2/PMS2 (n = 1), MLH1 (n = 1), MSH2 (n = 2), MSH6 (n = 6) and PMS2 (n = 6). All six prostatic neoplasms with dMMR had loss of MSH2/MSH6 (p < 0.0001). We conclude that neoplasms with positive results for TMB/MSI are highly concordant with positive dMMR results. Genetic/epigenetic alterations in the MMR genes are an underlying reason for most positive findings. The association of MSH2/MSH6 loss with prostatic neoplasms is of in-terest, but sample size is limited, and further studies are warranted to address this association.</p>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"290-291 ","pages":"44-50"},"PeriodicalIF":1.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142865988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognosis prediction and drug guidance of ovarian serous cystadenocarcinoma through mitochondria gene-based model.","authors":"Dongsheng Shen, Chenghao Wu, Meiyi Chen, Zixuan Zhou, Huaifang Li, Xiaowen Tong, Zhenghu Chen, Yi Guo","doi":"10.1016/j.cancergen.2024.12.005","DOIUrl":"https://doi.org/10.1016/j.cancergen.2024.12.005","url":null,"abstract":"<p><strong>Background: </strong>Mitochondrial dysregulation contributes to the chemoresistance of multiple cancer types. Yet, the functions of mitochondrial dysregulation in Ovarian serous cystadenocarcinoma (OSC) remain largely unknown.</p><p><strong>Aim: </strong>We sought to investigate the function of mitochondrial dysregulation in OSC from the bioinformatics perspective. We aimed to establish a model for prognosis prediction and chemosensitivity evaluation of the OSC patients by targeting mitochondrial dysregulation.</p><p><strong>Methods: </strong>Differentially expressed genes (DEGs) were screened from the Cancer Genome Atlas (TCGA)-OV dataset and the mitochondrial-related DEGs were identified from the Human MitoCarta 3.0 database. Prognosis-related mitochondria-related genes (MRGs) were screened to establish the MRGs-based risk score model for prognosis prediction. To validate the risk score model, the risk score model was then evaluated by IHC staining intensity and survival curves from clinical specimens of OSC patients. Migration and proliferation assays were performed to elucidate the role of carcinogenic gene ACSS3 in serous ovarian cancer cell lines.</p><p><strong>Results: </strong>Using consensus clustering algorithm, we identified 341 MRGs and two subtypes of OSC patients. Moreover, we established a novel prognostic risk score model by combining the transcription level, intensity and extent scores of MRGs for prognosis prediction purpose. The model was established using 7 MRGs (ACOT13, ACSS3, COA6, HINT2, MRPL14, NDUFC2, and NDUFV2) significantly correlated to the prognosis of OSC. Importantly, by performing the drug sensitivity analysis, we found that the OSC patients in the low-risk group were more sensitive to cisplatin, paclitaxel and docetaxel than those in the high-risk group, while the latter ones were more sensitive to VEGFR inhibitor Axitinib and BRAF inhibitors Vemurafenib and SB590885. In addition, patients in the low-risk group were predicted to have better response in anti-PD-1 immunotherapy than those in the high-risk group. The risk score model was then validated by survival curves of high-risk and low-risk groups determined by IHC staining scores of OSC clinical samples. The carcinogenic effect of ACSS3 in OSC was confirmed through the knockdown of ACSS3 in SKOV3 and HO-8910 cells.</p><p><strong>Conclusion: </strong>To summarize, we established a novel 7 MRGs - based risk score model that could be utilized for prognosis prediction and chemosensitivity assessment in OSC patients.</p>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"292-293 ","pages":"1-13"},"PeriodicalIF":1.4,"publicationDate":"2024-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142928449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Progesterone decreases viability and up regulates membrane progesterone receptors expression on the human Chronic Myeloid Leukemia cell line","authors":"Vahid Bagheri ,&nbsp;Fateme Rezaei ,&nbsp;Razieh Alipour ,&nbsp;Nasrin Sereshki ,&nbsp;Vahid Ahmadipanah ,&nbsp;Mitra Rafiee","doi":"10.1016/j.cancergen.2024.10.006","DOIUrl":"10.1016/j.cancergen.2024.10.006","url":null,"abstract":"<div><div>Progesterone (P4) has an important effect (activatory or inhibitory) on cell proliferation. Although there is evidence of the impact of progesterone on sex-linked cancers, it can affect other cancer cells expressing P4 receptors (PRs). We evaluated the expression of membrane P4 receptors (mPRs) and the viability in progesterone-treated K562 cells to inspect the possible effects route of progesterone on this (CML) cancer cell line. K562 cells were exposed to various concentrations of progesterone or no exposure for 48 and 72 h. The percentage of viability and cells that expressed mPRα and mPRβ were evaluated by MTT test and flow cytometry respectively. Progesterone significantly increased the expression of mPRα and especially mPRβ on the surface of K562 cells and significantly decreased their viability (<em>p</em> ≤ 0.05). Progesterone can reduce viability in K562 cells. Our findings showed that progesterone affects its receptor expression on K562 cells. Thus it may influence the performance of K562 cells in addition to its direct effects on these cells (via binding to its receptors).</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"288 ","pages":"Pages 114-117"},"PeriodicalIF":1.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142631196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mutations of ARID1B, PIK3C2B, KMT2B, and FAT1 genes influence clinical outcome in newly diagnosed myeloma","authors":"Marta Morawska,&nbsp;Michał Kiełbus,&nbsp;Magdalena Paziewska,&nbsp;Monika Szelest,&nbsp;Agnieszka Karczmarczyk,&nbsp;Joanna Zaleska,&nbsp;Paulina Własiuk,&nbsp;Krzysztof Giannopoulos,&nbsp;Norbert Grząśko","doi":"10.1016/j.cancergen.2024.11.001","DOIUrl":"10.1016/j.cancergen.2024.11.001","url":null,"abstract":"<div><div>The study aimed to elucidate the mutational profile of patients with newly diagnosed multiple myeloma to understand correlations of alterations with clinical outcomes. A cohort of 20 patients was enrolled, and mutational analysis was conducted using the TruSight Oncology 500 DNA Kit. Identified genetic alterations were related to clinicopathologic features and treatment outcomes. A total of 724 high-quality variants were validated. All patients harbored mutations associated with the RTK-RAS pathway, with over half having alterations in PI3 K, NOTCH, and WNT pathways. Several gene mutations were associated with specific clinical characteristics and prognostic indicators, revealing a complex interplay between genetic alterations and myeloma type, standard prognostic indicators, biochemical parameters, and renal function. Genetic alterations significantly influencing progression-free survival concerned <em>PIK3C2B, ARID1B</em> genes, and concomitant mutations in <em>KMT2B, FAT1</em>, and <em>ARID1B</em>. The findings underscore the potential of gene mutation-based prognostic tools in enhancing clinical decision-making and suggest that further exploration of identified genetic markers could pave the way for improved prognostic stratification and targeted therapeutic interventions in multiple myeloma.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"288 ","pages":"Pages 118-125"},"PeriodicalIF":1.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142631193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel lynch syndrome kindred with hereditary adrenal cortical carcinoma","authors":"Kripa Ahuja ,&nbsp;Ranjit Goudar","doi":"10.1016/j.cancergen.2024.11.005","DOIUrl":"10.1016/j.cancergen.2024.11.005","url":null,"abstract":"<div><h3>Background</h3><div>Adrenal cortical carcinoma (ACC) is an extremely rare malignancy, and advanced ACC carries a very poor prognosis. Early detection is critical since early-stage disease can be cured with surgical resection. ACC can be seen in Lynch syndrome; this case and review of the literature provide insight as to the potential biological origin of this malignancy. Clinicians should be aware of this association and the potential impact on cancer screening in these kindreds.</div></div><div><h3>Case Presentation</h3><div>We describe a novel kindred with hereditary adrenal cortical carcinoma and the Muir- Torre syndrome, a phenotypic variant of Lynch syndrome that includes sebaceous neoplasms and visceral malignancies. We report a 59-year-old Caucasian man with an MSH2 deletion who was diagnosed with metastatic adrenal cortical carcinoma. The patient's brother also had a history of adrenal cortical carcinoma. The patient's cancer initially responded to immunotherapy with pembrolizumab. Somatic genetic testing performed on a tumor biopsy did not identify the germline MSH2 deletion.</div></div><div><h3>Conclusions</h3><div>A review of the literature identifies an association between germline MSH2 mutations and ACC, suggesting a potential biological basis for carcinogenesis. This case highlights the importance of ACC screening for patients with Lynch Syndrome and a family history of adrenal cortical carcinoma due to the high mortality from this malignancy. This case also highlights the importance of separate germline and somatic testing for patients with a concerning personal or family history of cancers.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"288 ","pages":"Pages 137-140"},"PeriodicalIF":1.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142688712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of two cases of Familial Adenomatous Polyposis with the same APC genotype and different phenotypes","authors":"Eva Spier ,&nbsp;Aashna Pandya ,&nbsp;Miranda Di Biase","doi":"10.1016/j.cancergen.2024.10.008","DOIUrl":"10.1016/j.cancergen.2024.10.008","url":null,"abstract":"<div><div>Familial adenomatous polyposis (FAP) is a colorectal cancer (CRC) predisposition syndrome characterized by the presence of numerous colorectal adenomatous polyps, resulting from a single germline, heterozygous, likely pathogenic/pathogenic (LP/P) variant in the <em>APC</em> gene, an important tumor suppressor encoding gene. Classic FAP is considered in individuals with a germline LP/P variant in <em>APC</em> and have ≥100 colorectal adenomatous polyps beginning on average in adolescence, while attenuated FAP typically presents with fewer colorectal adenomatous polyps (10-&lt;100 polyps) in adulthood. Both forms can feature extracolonic manifestations, such as desmoid tumors, thyroid cancer, and osteomas. Reported genotype-phenotype correlations in FAP provide valuable insights for healthcare providers, but variable expressivity persists even among individuals sharing a genotype.</div><div>In this case study, we report two patients with the same pathogenic <em>APC</em> variant [c.4348C&gt;T, p.Arg1450Ter] and different presentations and clinical findings. Case 1 describes a 21-year-old male with an extensive family history of cancer who was diagnosed with FAP at age 4. Case 2 describes a 22-year-old female with no family history who was diagnosed with FAP after she initially presented with a desmoid tumor. Despite genetic similarities, their clinical courses significantly differed, emphasizing the variable expressivity of FAP. These cases highlight the importance of individual management and surveillance, as genotype alone may not predict clinical outcomes. They also underscore the need for further research into factors that influence FAP expressivity.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"288 ","pages":"Pages 110-113"},"PeriodicalIF":1.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142606959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}