No Reversal of Demethylation after Azacitidine Treatment in Concordance with Poor Clinical Response.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4629-4629
Author(s):  
Huong Thi Thanh Tran ◽  
Hee Nam Kim ◽  
JaeSook Ahn ◽  
Il-Kwon Lee ◽  
Deok-Hwan Yang ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Clinical Response ◽  
Methylation Level ◽  
Tumor Suppressor Genes ◽  
Gene Mutations ◽  
Molecular Monitoring ◽  
Suppressor Genes ◽  
Promoter Dna Methylation ◽  
History Of ◽  
Promoter Dna

Abstract The epigenetic gene silencing associated with promoter DNA methylation is as powerful as gene mutations in functionally inactivating tumor suppressor genes. Thus, a non-intensive treatment may be changed the natural history of MDS for the first time by the demethylating agent, 5-aza-deoxycytidine (Decitabine) with silenced gene expression by reversal of p15 hypermethylation and protein expression in the bone marrow in MDS. The MS-MLPA (methylation-specific multiplex ligation-dependent probe amplification) ME-001B probemix (MRC-Holland) containing 25 tumor suppressor genes has been used to detect the methylation level in the peripheral blood samples of 29 MDS before azacitidine (Vidaza) and only 6 MDS after 3–5 courses of therapy. Patients that hypermethylated at least 1 gene were 7 of 29, either the common hypermethylating genes as p15, ESR1 or the previously known FHIT in MDS also have occurred. Only two patients except one patient related to either methylation level-reducing gene or removal methylated gene (putative demethylation reversal) have in concordance with clinical response in hematological evidence. Interestingly, three other patients were high methylation level persistently or additional methylated gene after treatment (putative demethylation no reversal or more severe), two patients of these are correspond with no clinical response and one is propensity to progressing leukemia. With IGSF4 gene hypermethylation, to the best of our knowledge, there was no report in MDS. Our results suggest that methylation level possibly contributes to the dignosistic, prognosistic and a molecular monitoring marker after treatment of Azacitidine.

Strategies to Re-Express Epigenetically-Silenced Tumor Suppressor Genes Converge on the Requirement for Inhibition of the Histone Methyltransferase SUV39H1.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3357-3357
Author(s):  
Asha Lakshmikuttyamma ◽  
Stuart Scott ◽  
David P. Sheridan ◽  
John DeCoteau ◽  
Ron Geyer
Keyword(s):  
Tumor Suppressor ◽  
Cell Lines ◽  
Tumor Suppressor Genes ◽  
Fold Increase ◽  
Dna Demethylation ◽  
Dna Hypermethylation ◽  
Suppressor Genes ◽  
Promoter Dna Methylation ◽  
Promoter Dna ◽  
E Cadherin

Abstract Gene silencing mediated by aberrant promoter DNA hypermethylation represents a key mechanism by which tumor suppressor gene expression is silenced in cancer and it is associated with multiple repressive histone modifications. Histone H3 lysine 9 (H3K9) methylation is a key repressive chromatin modification with important implications for regulating cell proliferation, differentiation, and gene expression. SUV39H1 is a methyltransferase that catalyzes the addition of trimethyl groups to H3K9. SUV39H1 is associated with regions of hypermethylated CpG islands, with repressive complexes, such as RB/E2F, and with DNA-binding proteins involved in leukemogenesis, such as AML1 and PML-RAR, where its H3K9 trimethylation activity promotes heterochromatin formation and gene silencing. We studied the requirement of SUV39H1 in the epigenetic silencing of heavily methylated tumor suppressor genes p15INK4B and E-cadherin in acute myeloid leukemia (AML). Treatment of AML cell lines AML193, KG1a, and Kasumi with the DNA methyltransferase (DNMT) inhibitor 5-Aza-2’-deoxycytidine (5-Aza-dC) induces p15INK4B and E-cadeherin re-expression in association with dramatic decreases in p15INK4B and E-cadherin promoter DNA methylation and marked reductions in the levels of SUV39H1 and H3K9 trimethylation at these promoters. Interestingly, treatment of these cell lines with SUV39H1 shRNA, or the SUV39H1 inhibitor chaetocin, also induces p15INK4B and E-cadherin re-expression and H3K9 demethylation, without affecting promoter DNA methylation. Thus, re-expression of hypermethylated tumor suppressors requires histone H3K9 demethylation, which can be achieved indirectly by decreasing the amount of SUV39H1 associated with the promoter using 5-Aza-dC, or directly by inhibiting SUV39H1 expression or activity without requiring promoter DNA demethylation. Furthermore, we found that SUV39H1 shRNA or chaetocin in combination with 5-Aza-dC acts synergistically to re-express epigenetically silenced p15INK4B and E-cadherin in AML cell lines. Treatment of primary human AML blasts obtained from two patients with combinations of 5-Aza-C and chaetocin also results in synergistic re-expression of p15INK4B and E-cadherin (2–6 fold increase with 5-Aza-C or chaetocin treatment vs. 11–14 fold increase with co-treatment). Our study has important implications for developing novel epigenetic therapies of relevance to AML as it suggests that the re-expression of tumor suppressor genes silenced by aberrant promoter DNA hypermethylation converges on the requirement for SUV39H1 and H3K9 methylation inhibition but not promoter DNA demethylation. Our finding that SUV39H1 inhibition may function synergistically with DNMT inhibitors to enhance gene reactivation and chromatin changes also highlights the needs for developing more inhibitors of histone methyltransferases and for performing detailed drug interaction studies to identify the best drug combinations for optimal epigenetic therapies.

Cooperation of Gene Mutations Including Class I, Class II and Tumor Suppressor Genes In Childhood Acute Myeloid Leukemia and Their Impacts on Survivals

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2713-2713
Author(s):  
Der-Cherng Liang ◽  
Lee-Yung Shih ◽  
Chao-Ping Yang ◽  
Iou-Jih Hung ◽  
Tang-Her Jaing ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Gene Mutation ◽  
Tumor Suppressor Genes ◽  
Chromosomal Abnormalities ◽  
Gene Mutations ◽  
Class Ii ◽  
Suppressor Gene ◽  
Class I ◽  
Suppressor Genes ◽  
Pediatric Aml

Abstract Abstract 2713 Background. The cooperation of gene mutations, especially their impacts on survivals of childhood acute myeloid leukemia (AML) has not been well known. Aims. Our aims were (1) to study the frequency of each gene mutation in childhood AML, (2) to study the impact of each gene mutation on the treatment outcome, and (3) to examine the cooperativity of gene mutations. Materials and Methods. From Feb. 1996 to Jan. 2010, bone marrow samples at diagnosis from 198 children with AML at Chang Gung Children's Hospital, Taoyuan and Mackay Memorial Hospital, Taipei, were analyzed for gene mutations including FLT3-ITD, FLT3-TKD (D835), c-KIT, cFMS, JAK 2V617F, NRAS, KRAS, PTPN11 (Class I mutations), RUNX1, CEBPα, NPM1 (Class II mutations), WT1 and P53 (tumor suppressor genes). The subtypes included: t(8;21) 19.9%, inv(16) 8.9%, t(15;17) 8.4%, t(9;11) 5.2%, t(10;11) 2.6%, trisomy 21 4.2%, intermediate-risk group 40.3% (including 13 patients with other MLL translocations), and poor-risk group 11.0% (including 7 patients with complex chromosomal abnormalities and 4 patients with MLL-PTD). Results. FLT3-ITD occurred in 15.0% of patients, FLT3-TKD 7.2%, c-KIT 11.5%, c-FMS 2.9%, JAK2V617F 3.3%, NRAS 9.1%, KRAS 7.7%, PTPN11 3.3%, RUNX1 2.7%, CEBPα 7.9%, NPM1 4.1%, WT1 3.9% and P53 1.7%. Taken together, 52.5% of patients had Class I gene mutations, 13.1% had Class II gene mutations, and 5.1% had WT1 or P53 mutations. In all, 59.1% of patients had Class I, Class II or tumor suppressor gene mutations. Only one patient (0.5 %) had gene mutations involving all Class I, Class II and tumor suppressor genes. Ninety-eight patients, who were treated with Taiwan Pediatric Oncology Group (TPOG) APL protocols (for acute promyelocytic leukemia) and TPOG 97A protocol (for other AML) (Liang et al, Leukemia 2006), were analyzed for survivals. In patients with t(8;21), the 5-year event-free survival (EFS) was 66±12%; 71±17% for patients with c-KIT mutations and 50±35% for the 2 patients with JAK2V617F. In patients with inv(16), the EFS of 70±15% seemed to be compromised (60±22%) for those with c-KIT mutations. In patients with t(15;17), the EFS of 78±11% was not compromised by FLT3-ITD or FLT3-TKD mutations. In patients with t(9;11), the EFS of 64% seemed to be compromised (50±35%) in the 2 patients with FLT3-TKD mutations. In 3 patients with t(10;11), no gene mutations were found. In trisomy 21, the EFS of 75±22% seemed to be compromised (50±35%) in the 2 patients with CEBPα mutations. Of the 5 patients with complex chromosomal abnormalities, the only one patient carrying RUNX1 survived. Of the 3 patients with MLL-PTD having an EFS of 33±27%, one each patient with c-FMS or WT1 mutation died. The only one patient who had all Class I, Class II and tumor suppressor gene mutations (FLT3-TKD+ CEBPα+ WT1) died in induction therapy. Two of the other 4 patients who had 3 mutations acrossing 2 classes had EFS of 6 and 10 months, respectively. Conclusions. Our study on a large cohort of pediatric AML patients revealed that 59.1% patients had at least one gene mutation. That 3 of 5 patients who had 3 gene mutations soon failed suggested that gene mutations, especially in 3 combinations, might compromise the survival. Further study on more patients is warranted to explore more of the prognostic significance of cooperating gene mutations in pediatric AML. (Supported by grants MMH-E-98009, NSC 96–2314-B-195-006-MY3, NHRI-EX-96-9434SI and DOH99-TD-C-111-006.) Disclosures: No relevant conflicts of interest to declare.

scholarly journals Screening of Tumor Suppressor Genes in Metastatic Colorectal Cancer

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Lu Qi ◽  
Yanqing Ding
Keyword(s):  
Colorectal Cancer ◽  
Tumor Suppressor ◽  
Mrna Expression ◽  
Binding Site ◽  
Methylation Level ◽  
Tumor Suppressor Genes ◽  
Enrichment Analysis ◽  
Suppressor Genes ◽  
Genes Expression ◽  
Chromosome 17P13

Most tumor suppressor genes are commonly inactivated in the development of colorectal cancer (CRC). The activation of tumor suppressor genes may be beneficial to suppress the development and metastasis of CRC. This study analyzed genes expression and methylation levels in different stages of CRC. Genes with downregulated mRNA expression and upregulated methylation level in advanced CRC were screened as the potential tumor suppressor genes. After comparing the methylation level of screened genes, we found that MBD1 gene had downregulated mRNA expression and upregulated methylation levels in advanced CRC and continuously upregulated methylation level in the progression of CRC. Enrichment analysis revealed that genes expression in accordance with the elevated expression of MBD1 mainly located on chromosomes 17p13 and 17p12 and 8 tumor suppressor genes located on chromosome 17p13. Further enrichment analysis of transcription factor binding site identified that SP1 binding site had higher enrichment and could bind with MBD1. In conclusion, MBD1 may be a tumor suppressor gene in advanced CRC and affect the development and metastasis of CRC by regulating 8 tumor suppressor genes through binding with SP1.

Establishment of Myelodysplastic Syndrome-Specific Methylome: Implications for the Pathogenesis of Clonal Evolution and Association with Survival

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 850-850
Author(s):  
Rrebecca D ganetzky ◽  
Ying Jiang ◽  
Courtney Prince ◽  
Mikkael A. Sekeres ◽  
Yogen Saunthararajah ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Methylation Level ◽  
Tumor Suppressor Genes ◽  
Methylation Status ◽  
Methylation Pattern ◽  
Epigenetic Silencing ◽  
Methylation Analysis ◽  
Suppressor Genes ◽  
Cpg Sites ◽  
Disease Specific

Abstract Epigenetic silencing of genes, such as tumor suppressor genes (TSG), throughaberrant promoter hypermethylation has been implicated in the pathogenesis of MDS. Epigenetic silencing may cooperate with chromosomal abnormalities to completelysilence a TSG or duplication of methylated alleles through UPD could potentially leadto complete TSG silencing. Hypomethylating agents can reverse aberrant silencing;however targeted application of epigenetic therapy is not possible, as ypermethylatedsites relevant to MDS pathogenesis remain mostly unknown. Traditional echnologieslimited methylation analysis to a small number of individual loci; as a result, there has been a lack of systematic studies on the methylation pattern in MDS. New methylationarray techniques allow for rapid polygenic analysis of methylation and the stablishmentof tissue- and disease-specific methylomes. We hypothesized that using ethylationarrays (Illumina®) aberrantly hypermethylated CpG sites and whole methylation patternspathognomic for MDS can be identified. First, we compared patients with MDS andAML (n=240) to controls (n=64) using low-density methylation arrays (1,505 CpG sites)to explore the general applicability of whole genome methylation arrays. We hen usedhigh density arrays (27,578 CpG sites) to fully explore a disease-specific ethylome in a representative sub-cohort of MDS/AML patients. We developed ananalytic algorithm that included establishment of the methylome of normal marrow as a reference and analysis of concordantly hypermethylated genes in patients, using methylation status as either a continuous or dichotomized variable. Global methylation analysis demonstrated that there was concordant hypermethylation in 25% and 50% of MDS patients in 1,199 CpG and 93 CpG sites, respectively, and in 25% and 50% of high-risk MDS patients at 1,816 and 288 CpG sites, respectively. The average methylation level was significantly higher in MDS than in controls and was associated with IPSS score (p=.06). The methylation pattern in MDS include aberrant hypermethylation of tumor suppressor genes (DCC, HIC1), and genes involved in DNA repair (OGG1, MGMT), cell cycle control (DBC1), development and differentiation (HOXA5, HOXB6) and apoptosis (ALOX12). Analysis of the most frequently aberrantly methylated genes identified several genes and we used FZD9 as a candidate TSG on chromosome 7 as an illustrative example for further analysis. Methylation level at this site was significantly predictive of survival in proportional hazards regression analysis (p=.002) and inversely correlated with expression of FZD9 mRNA. Using high density arrays to examine methylation status at locations most commonly associated with chromosomal lesions in MDS (chromosome 5, 7, 11, 13 and 20), we discovered 8 genes with functions and tissue expression patterns suggestive of involvement with MDS. Of these genes, 7 have previously been reported to be aberrantly hypermethylated in malignancy. Patients who did not exhibit hypermethylation at any of these sites were less likely to have developed AML (OR = 4.2, p = 0.074) and showed prolonged survival (p =.09). The absence of hypermethylation at one of the 8 pathognomonic sites was significantly predictive of survival (p=.05). In conclusion, genetic silencing by hypermethylation can produce molecular phenotypes identical to loss of function mutations and deletion of genetic information; however, unlike genetic lesions, epigenetic lesions are more common and are reversible by hypomethylating therapy. Development of a predictive algorithm based on methylation data will allow targeted therapy with epigenetic therapies.

ABERRANT DNA METHYLATION AS A CANCER-INDUCING MECHANISM

2005 ◽  
Vol 45 (1) ◽  
pp. 629-656 ◽  
Author(s):  
Manel Esteller
Keyword(s):  
Dna Methylation ◽  
Tumor Suppressor ◽  
Tumor Suppressor Genes ◽  
Cpg Island ◽  
Gene Mutations ◽  
Promoter Hypermethylation ◽  
Dna Methyltransferases ◽  
Tumor Type ◽  
Suppressor Genes ◽  
Aberrant Dna Methylation

Aberrant DNA methylation is the most common molecular lesion of the cancer cell. Neither gene mutations (nucleotide changes, deletions, recombinations) nor cytogenetic abnormalities are as common in human tumors as DNA methylation alterations. The most studied change of DNA methylation in neoplasms is the silencing of tumor suppressor genes by CpG island promoter hypermethylation, which targets genes such as p16INK4a, BRCA1, and hMLH1. There is a profile of CpG island hypermethylation according to the tumor type, and genes silent by methylation represent all cellular pathways. The introduction of bisulfite-PCR methodologies combined with new genomic approaches provides a comprehensive spectrum of the genes undergoing this epigenetic change across all malignancies. However, we still know very little about how this aberrant DNA methylation “invades” the previously unmethylated CpG island and how it is maintained through cell divisions. Furthermore, we should remember that this methylation occurs in the context of a global genomic loss of 5-methylcytosine (5mC). Initial clues to understand this paradox should be revealed from the current studies of DNA methyltransferases and methyl CpG binding proteins. From the translational standpoint, we should make an effort to validate the use of some hypermethylated genes as biomarkers of the disease; for example, it may occur with MGMT and GSTP1 in brain and prostate tumors, respectively. Finally, we must expect the development of new and more specific DNA demethylating agents that awake these methyl-dormant tumor suppressor genes and prove their therapeutic values. The expectations are high.

scholarly journals Frequent Loss of Heterozygosity on Chromosomes 3p and 17p without VHL or p53 Mutations Suggests Involvement of Unidentified Tumor Suppressor Genes in Follicular Thyroid Carcinoma1

1997 ◽  
Vol 82 (11) ◽  
pp. 3684-3691
Author(s):  
Stefan K. G. Grebe ◽  
Bryan McIver ◽  
Ian D. Hay ◽  
Patricia S.-C. Wu ◽  
Lea M. Z. Maciel ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Thyroid Carcinoma ◽  
Loss Of Heterozygosity ◽  
Tumor Suppressor Genes ◽  
Average Rate ◽  
Gene Mutations ◽  
Follicular Adenoma ◽  
Papillary Thyroid ◽  
P53 Mutations ◽  
Suppressor Genes

Follicular thyroid carcinoma (FTC) exhibits frequent loss of heterozygosity (LOH) on chromosomes 10q and 3p, suggesting involvement of tumor suppressor genes. We screened 14 FTC (10 Hurthle cell carcinomas and 4 nonoxyphilic FTC), 14 papillary thyroid carcinomas, and 7 follicular adenomas for LOH on chromosome arms 1p, 3p, 3q, 10p, 10q, 11p, 11q, 13q, 17p, and 17q. LOH was more frequent in FTC than in follicular adenoma or papillary thyroid carcinoma. In FTC, rates of LOH on 3p (86%), 17p (72%), and 10q (57%) were higher than the average rate of LOH (33%; P < 0.05). Most frequently involved were 3p21–25 and 17p13.1–13.3, the sites for the VHL (3p25–26) and p53 (17p13.1) tumor suppressors. We, therefore, characterized these genes by dideoxy fingerprinting and DNA sequencing. Two FTC had mutations in p53, but only 1 of these exhibited LOH at 17p. No VHL gene mutations were found. Thus, neither p53 nor VHL genes play a significant role in the pathogenesis of differentiated thyroid cancer. LOH on 17p, but not on 3p or 10q, was correlated with mortality. Accordingly, 3p and 10q LOH may represent early, and 17p LOH late, events in FTC development. The data suggest the presence of novel tumor suppressor genes on chromosomes 3p and 17p that may be important in the pathogenesis of FTC.

scholarly journals Metallothioneins Gene Regulation Through Promoter DNA Methylation According to Zn and Cu Trace Elements Status in Human Hepatocellular Carcinoma (P05-002-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Domenica De Santis ◽  
Silvia Udali ◽  
Filippo Mazzi ◽  
Andrea Ruzzenente ◽  
Greta Beschin ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Dna Methylation ◽  
Trace Elements ◽  
Tumor Suppressor ◽  
Tumor Suppressor Genes ◽  
Funding Sources ◽  
Promoter Dna Methylation ◽  
Serum Trace Elements ◽  
Promoter Dna

Abstract Objectives Hepatocellular carcinoma (HCC) is the most frequent primary liver cancer, yet mechanisms of hepatocarcinogenesis are largely unknown. A particular interest was recently dedicated to the role of trace elements and metallothioneins (MTs), a group of proteins involved in metal ions homeostasis and detoxification, have been suggested as possible tumor suppressor genes. The study of MTs transcriptional regulation by promoter DNA methylation is the object of study as a possible mechanism responsible for gene silencing through epigenetics. Methods Twenty-seven HCC patients undergoing surgery intervention were enrolled and clinically characterized. MT1G and MT1H gene expression was performed by Real Time qPCR. DNA methylation analysis in 23 HCC and homologous non-neoplastic liver tissue (N) was performed by Bisulfite-Amplicon Sequencing (BSAS) in an overlapping region (∼400 bp) of the promoters of the two genes. Cu and Zn concentrations were measured in serum and liver tissues (HCC and N) by Inductively Coupled Plasma Mass Spectrometry (ICP-MS). Kaplan-Meier analysis of survival was performed according to serum trace elements. Results MT1G and MT1H were transcriptionally repressed in HCC tissue as compared to N. A correlation was observed between the mRNA levels of the two MTs, in particular MT1G was repressed in 23 out of 27 HCC tissue (P = 0.0366) and MT1H was repressed in 24 out of 27 HCC tissue (P = 0.0077). The promoter region resulted hypermethylated in 9 out of 19 HCC that showed MT1G and MT1H down-regulation. Serum Zn and Cu levels were within the normal range while HCC tissue exhibited significantly reduced Zn levels as compared to N (P < 0.0001). Tissue Cu levels did not show significant differences. Serum trace elements levels were also analyzed according to patients clinical features and those with Cu levels higher than the 75th percentile had a significantly poorer prognosis than those within the lowest Cu levels quartile (P < 0.05). Conclusions MT1G and MT1H are repressed in HCC tissue. In a subset of patients the downregulation was associated to promoter hypermethylation, supporting the hypothesis of MT1G and MT1H as possible tumor suppressor genes in HCC. Evidence of a correlation between serum Cu levels and survival rate provide new insights for the role of this microelement in liver carcinogenesis. Funding Sources No funding sources.

scholarly journals Perspectives and Issues in the Assessment of SMARCA4 Deficiency in the Management of Lung Cancer Patients

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1920
Author(s):  
Subasri Armon ◽  
Paul Hofman ◽  
Marius Ilié
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Tumor Suppressor ◽  
Cancer Patients ◽  
Tumor Suppressor Genes ◽  
Gene Mutations ◽  
Small Cell ◽  
Small Cell Lung ◽  
Suppressor Genes ◽  
Lung Cancer Patients

Lung cancers are ranked third among the cancer incidence in France in the year 2020, with adenocarcinomas being the commonest sub-type out of ~85% of non-small cell lung carcinomas. The constant evolution of molecular genotyping, which is used for the management of lung adenocarcinomas, has led to the current focus on tumor suppressor genes, specifically the loss of function mutation in the SMARCA4 gene. SMARCA4-deficient adenocarcinomas are preponderant in younger aged male smokers with a predominant solid morphology. The importance of identifying SMARCA4-deficient adenocarcinomas has gained interest for lung cancer management due to its aggressive behavior at diagnosis with vascular invasion and metastasis to the pleura seen upon presentation in most cases. These patients have poor clinical outcome with short overall survival rates, regardless of the stage of disease. The detection of SMARCA4 deficiency is possible in most pathology labs with the advent of sensitive and specific immunohistochemical antibodies. The gene mutations can be detected together with other established lung cancer molecular markers based on the current next generation sequencing panels. Sequencing will also allow the identification of associated gene mutations, notably KRAS, KEAP1, and STK11, which have an impact on the overall survival and progression-free survival of the patients. Predictive data on the treatment with anti-PD-L1 are currently uncertain in this high tumor mutational burden cancer, which warrants more groundwork. Identification of target drugs is also still in pre-clinical testing. Thus, it is paramount to identify the SMARCA4-deficient adenocarcinoma, as it carries worse repercussions on patient survival, despite having an exceptionally low prevalence. Herein, we discuss the pathophysiology of SMARCA4, the clinicopathological consequences, and different detection methods, highlighting the perspectives and challenges in the assessment of SMARCA4 deficiency for the management of non-small cell lung cancer patients. This is imperative, as the contemporary shift on identifying biomarkers associated with tumor suppressor genes such as SMARCA4 are trending; hence, awareness of pathologists and clinicians is needed for the SMARCA4-dNSCLC entity with close follow-up on new management strategies to overcome the poor possibilities of survival in such patients.

Sign in / Sign up

Export Citation Format

Share Document