Cancer Genetics最新文献

{"title":"Diagnostic and prognostic potential of FBXO8 expression in kidney renal clear cell carcinoma and its regulation of renal adenocarcinoma cells","authors":"Zhouan Luo ,&nbsp;Xiaoping Wu ,&nbsp;Juanxia Xie ,&nbsp;Hao Tang ,&nbsp;Jingqi Chen ,&nbsp;Dongcai Ye ,&nbsp;Shangwen Dou ,&nbsp;Songning Chen","doi":"10.1016/j.cancergen.2024.11.004","DOIUrl":"10.1016/j.cancergen.2024.11.004","url":null,"abstract":"<div><h3>Background</h3><div>The F-box protein 8 Gene (<em>FBXO8</em>) 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.</div></div><div><h3>Methods</h3><div>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 <em>FBXO8</em> gene expression and its impact on survival. Clinical characteristics were classified, and <em>FBXO8</em> 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 <em>FBXO8</em> 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.</div></div><div><h3>Results</h3><div>Our findings revealed decreased <em>FBXO8</em> expression in KIRC, with patients exhibiting low <em>FBXO8</em> expression experiencing shorter survival times. The low expression group showed elevated TME immune and estimate scores. Biofunctional analyses indicated that <em>FBXO8</em> 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 <em>FBXO8</em> expression and immune cell infiltration, as well as checkpoints such as <em>CD274</em>. 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.</div></div><div><h3>Conclusion</h3><div>This study demonstrates that <em>FBXO8</em> serves as a biomarker for KIRC and plays a role in regulating cell proliferation, migration, and apoptosis.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"290 ","pages":"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 ,&nbsp;Hector Alvarez ,&nbsp;Antony San Lucas ,&nbsp;Sinchita Roy-Chowdhuri ,&nbsp;Asif Rashid ,&nbsp;Hui Chen ,&nbsp;Leomar Y. Ballester ,&nbsp;Keith Sweeney ,&nbsp;Mark J. Routbort ,&nbsp;Keyur P. Patel ,&nbsp;Rajyalakshmi Luthra ,&nbsp;L Jeffrey Medeiros ,&nbsp;Gokce A. Toruner","doi":"10.1016/j.cancergen.2024.12.002","DOIUrl":"10.1016/j.cancergen.2024.12.002","url":null,"abstract":"<div><div>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).</div><div>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</div><div>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 (<em>n</em> = 59) or TMB-High/MSI-Undetermined (<em>n</em> = 6) results as well as concurrent IHC results for MMR proteins [colorectal (<em>n</em> = 25), endometrial (<em>n</em> = 28), prostatic (<em>n</em> = 7), urothelial (<em>n</em> = 3), other (<em>n</em> = 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 (<em>n</em> = 33), MSH2/MSH6 (<em>n</em> = 14), MLH1/MSH2/PMS2 (<em>n</em> = 1), MLH1 (<em>n</em> = 1), MSH2 (<em>n</em> = 2), MSH6 (<em>n</em> = 6) and PMS2 (<em>n</em> = 6). All six prostatic neoplasms with dMMR had loss of MSH2/MSH6 (<em>p</em> &lt; 0.0001).</div><div>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</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"290 ","pages":"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 ,&nbsp;Chenghao Wu ,&nbsp;Meiyi Chen ,&nbsp;Zixuan Zhou ,&nbsp;Huaifang Li ,&nbsp;Xiaowen Tong ,&nbsp;Zhenghu Chen ,&nbsp;Yi Guo","doi":"10.1016/j.cancergen.2024.12.005","DOIUrl":"10.1016/j.cancergen.2024.12.005","url":null,"abstract":"<div><h3>Background</h3><div>Mitochondrial dysregulation contributes to the chemoresistance of multiple cancer types. Yet, the functions of mitochondrial dysregulation in Ovarian serous cystadenocarcinoma (OSC) remain largely unknown.</div></div><div><h3>Aim</h3><div>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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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 (<em>ACOT13, ACSS3, COA6, HINT2, MRPL14, NDUFC2,</em> and <em>NDUFV2</em>) 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.</div></div><div><h3>Conclusion</h3><div>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.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"292 ","pages":"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":"OA","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}

{"title":"Contribution of ERCC2 rs13181 (Lys751Gln) and rs1799793 (Asp312Asn) polymorphisms to the risk of bladder cancer in Bangladesh","authors":"Md. Ariful Islam ,&nbsp;Saima Mubashshira ,&nbsp;Md. Mostafijur Rahman ,&nbsp;Yearul Kabir","doi":"10.1016/j.cancergen.2024.11.002","DOIUrl":"10.1016/j.cancergen.2024.11.002","url":null,"abstract":"<div><h3>Background</h3><div>Human Excision Repair Cross-Complementation Group 2 (ERCC2) proteins play a vital role in the nucleotide excision repair pathway through ATP-dependent helicase activity. Several studies found that polymorphisms in the ERCC2 gene are associated with susceptibility to different cancers, although the outcomes were confusing.</div></div><div><h3>Objective</h3><div>As a result, in this retrospective study, we investigated the relationship between genetic polymorphisms of the ERCC2 gene at codons 312 (rs1799793) and 751 (rs13181) and bladder cancer susceptibility in Bangladesh, as well as the disease's aggressiveness.</div></div><div><h3>Methods</h3><div>Genetic polymorphisms of ERCC2 were assayed by the polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) method with 121 bladder cancer patients and 130 healthy controls.</div></div><div><h3>Results</h3><div>Patients who had the Gln/Gln polymorphism of ERCC2 at codon 751 (OR=3.27; 95% CI=1.19-8.67; p&lt;0.05) and Asp/Asn at codon 312 (OR=2.14; 95% CI=1.03-4.29; p&lt;0.05) were significantly associated with a higher risk of developing bladder cancer. Again, Gln/Gln polymorphisms in bladder cancer (p&lt;0.05) were more likely to be present in individuals with cancer in the family.</div></div><div><h3>Conclusions</h3><div>This study reveals that susceptibility and bladder cancer aggressiveness are associated with polymorphisms at codon 751 and Asp/Asn at codon 312 of the ERCC2 gene.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"288 ","pages":"Pages 126-132"},"PeriodicalIF":1.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142649458","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 profiling of metastatic colon adenocarcinoma in Iranian patients: Insights into pathogenic variants and tumor characteristics","authors":"Parnian Boroonsara ,&nbsp;Reza Jafarzadeh Esfehani ,&nbsp;Ali Taghizadeh Kermani ,&nbsp;Naeeme shakour","doi":"10.1016/j.cancergen.2024.11.003","DOIUrl":"10.1016/j.cancergen.2024.11.003","url":null,"abstract":"<div><h3>Introduction</h3><div>Colorectal cancer (CRC) remains one of the leading causes of cancer-related mortality, and understanding the genetic landscape is crucial for improving targeted therapies. This study aimed to analyze the tumor's genetic profiles of patients with metastatic CRC, focusing on pathogenic or likely pathogenic variants in tumor related genes.</div></div><div><h3>Materials and Methods</h3><div>The present cross-sectional study was conducted on 40 Persian patients with metastatic colorectal adenocarcinoma. Formalin-fixed paraffin-embedded tumor samples were analyzed using next generation sequencing technique to detect pathogenic variants. The patients' tumor characteristics, including differentiation grades and tumor sites (colon, rectum, or rectosigmoid), were documented and the relationship between variants and tumor characteristics was evaluated.</div></div><div><h3>Results</h3><div>The study population had a mean age of 55.75 ± 12.88 years, and 60 % were female. The most common tumor site was the colon (52.5 %), followed by rectosigmoid (27.5 %) and cecum (20 %). <em>APC</em> gene variants were prevalent in 72.5 % of patients, with the p.Arg876* variant being the most frequent. <em>TP53</em> gene variants were present in 65 %, with p.Trp146* and p.Arg273His being the most common. Pathogenic <em>KRAS</em> gene variants were observed in 50 %, significantly associated with rectosigmoid involvement (<em>p</em> = 0.001). The <em>ERBB2</em> CNVs were found in 25 % of patients and were associated with colon involvement (<em>p</em> = 0.021).</div></div><div><h3>Conclusion</h3><div>The study highlights the genetic diversity in Persian patients with metastatic colon adenocarcinoma and demonstrated that <em>APC</em> and TP53 variants were the most prevalent, while <em>KRAS</em> and <em>ERBB2</em> variants were associated with specific tumor sites. These findings provide a basis for personalized treatment strategies in CRC among Persian population.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"288 ","pages":"Pages 133-136"},"PeriodicalIF":1.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142683193","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":"Recurrent cytogenetic abnormalities reveal alterations that promote progression and transformation in myelodysplastic syndrome","authors":"Rolando García,&nbsp;Tasnim Alkayyali,&nbsp;Luis Mosquera Gomez,&nbsp;Carter Wright,&nbsp;Weina Chen,&nbsp;Dwight Oliver,&nbsp;Prasad Koduru","doi":"10.1016/j.cancergen.2024.10.002","DOIUrl":"10.1016/j.cancergen.2024.10.002","url":null,"abstract":"<div><h3>Objective</h3><div>To illustrate patterns of cytogenetic abnormalities that promote progression and/or transformation in myelodysplastic syndrome.</div></div><div><h3>Methods</h3><div>In this study we evaluated three different data sets to identify recurrent cytogenetic abnormalities (RCAs) to delineate the cytogenetic evolutionary trajectories and their clinical significance.</div></div><div><h3>Results</h3><div>Datasets 1 and 2 were 2402 cross sectional samples from Mitelman database of Chromosome Aberrations and Gene Fusions in Cancer; these were used to discover RCAs and to validate them. Dataset 3 was a cohort of 163 institutional patients with serial samples from 35 % of them. This was used to further validate RCAs identified in the cross-sectional data, and their clinical impact. We identified MDS subtype associated RCAs, and some exclusive RCAs (Xp-, 2q-, 17q-, 21q-) that led to disease progression or transformation to leukemia. Evolutionary pathway analysis had shown temporal acquisition of RCAs. Therefore, presence of two or more RCAs suggests cooperative or complementary role in disease progression or transformation. Patients with one or more of these RCAs had poor prognosis and high risk for transformation. Genes frequently altered in MDS are mapped to some of the RCAs and suggest a close correlation between RCAs and molecular alterations in MDS. Karyotypic complexity, clonal evolution, loss of 17p had poor clinical outcomes.</div></div><div><h3>Conclusion</h3><div>This study identified a unique combination of RCAs that are components in distinct cytogenetic trajectories. Some of these were primary changes while others were secondary or tertiary changes. Acquiring specific additional aberrations predicts progression or transformation to leukemia.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"288 ","pages":"Pages 92-105"},"PeriodicalIF":1.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142578229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}