MUC17 mutations and methylation are associated with poor prognosis in adult-type diffuse glioma patients

Machado, Gabriel Cardoso; Ferrer, Valéria Pereira

doi:10.1016/j.jns.2023.120762

Cited by 9 publications

(7 citation statements)

References 87 publications

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“…A previous study reported that ZNF750 was a tumor suppressor, and the mutant ZNF750 promoted cell proliferation, foci formation, migration, and xenograft tumor growth in multiple squamous cell carcinomas [ 39 ]. MUC17 mutations was associated with poor prognosis in glioma cohorts [ 40 ]. It is possible that those mutations occurring at key transitional points will promote extensive mutagenesis and the development of invasive carcinoma [ 41 ].…”

Section: Resultsmentioning

confidence: 99%

Genomic characterization and risk stratification of esophageal squamous dysplasia

Min,

Zhang,

Lin

et al. 2024

Medical Review

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Objectives The majority of esophageal squamous dysplasia (ESD) patients progress slowly, while a subset of patients can undergo recurrence rapidly or progress to invasive cancer even after proper treatment. However, the molecular mechanisms underlying these clinical observations are still largely unknown. Methods By sequencing the genomic data of 160 clinical samples from 49 tumor-free ESD patients and 88 esophageal squamous cell carcinoma (ESCC) patients, we demonstrated lower somatic mutation and copy number alteration (CNA) burden in ESD compared with ESCC. Results Cross-species screening and functional assays identified ACSM5 as a novel driver gene for ESD progression. Furthermore, we revealed that miR-4292 promoted ESD progression and could serve as a non-invasive diagnostic marker for ESD. Conclusions These findings largely expanded our understanding of ESD genetics and tumorigenesis, which possessed promising significance for improving early diagnosis, reducing overtreatment, and identifying high-risk ESD patients.

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Section: Resultsmentioning

confidence: 99%

Genomic characterization and risk stratification of esophageal squamous dysplasia

Min,

Zhang,

Lin

et al. 2024

Medical Review

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“… 9 Contrary to our findings, a recent multi-database glioblastoma analysis found that MUC17 mutations were associated with poorer prognosis. 10 In breast cancer, MUC17 knockdown improved chemosensitivity in vitro, while in lung cancer, decreased MUC17 expression was observed in tyrosine kinase inhibitor (TKI) resistance. 11 , 12 Given that EGFR TKIs have been trialed in glioblastoma with little success, the possibility that MUC17 activity relates to TKI resistance may warrant further exploration.…”

Section: Discussionmentioning

confidence: 99%

Profiling the molecular and clinical landscape of glioblastoma utilizing the Oncology Research Information Exchange Network brain cancer database

Demetriou,

Chow,

Craig

et al. 2024

Neuro-Oncology Advances

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Background Glioblastoma exhibits aggressive growth and poor outcomes despite treatment, and its marked variability renders therapeutic design and prognostication challenging. The Oncology Research Information Exchange Network (ORIEN) database contains complementary clinical, genomic, and transcriptomic profiling of 206 glioblastoma patients, providing opportunities to identify novel associations between molecular features and clinical outcomes. Methods Survival analyses were performed using the Logrank test, and clinical features were evaluated using Wilcoxon and chi-squared tests with q-values derived via Benjamini-Hochberg correction. Mutational analyses utilized sample-level enrichments from whole exome sequencing data, and statistical tests were performed using the one-sided Fisher Exact test with Benjamini-Hochberg correction. Transcriptomic analyses utilized a student’s t-test with Benjamini-Hochberg correction. Expression fold changes were processed with Ingenuity Pathway Analysis to determine pathway-level alterations between groups. Results Key findings include an association of MUC17, SYNE1 and TENM1 mutations with prolonged overall survival (OS); decreased OS associated with higher EGFR mRNA expression, but not with EGFR amplification or mutation; a 14-transcript signature associated with OS >2 years; and two transcripts associated with OS <1 year. Conclusion Herein, we report the first clinical, genomic, and transcriptomic analysis of ORIEN glioblastoma cases, incorporating sample reclassification under updated 2021 diagnostic criteria. These findings create multiple avenues for further investigation and reinforce the value of multi-institutional consortia such as ORIEN in deepening our knowledge of intractable diseases such as glioblastoma.

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“…A high mutation frequency for MUC17 and TTN have recently been reported as an unexpected finding in a study of early onset breast cancer (EOBC) in Taiwanese women (Midha et al, 2020). MUC17 may influence chemoresistance and has recently been reported as a driver gene in adult gliomas (Al Amri et al, 2020; Machado & Ferrer, 2023). For TTN , Oh et al (2020) found that mutations in TTN correlate with tumor mutational burden and high microsatellite instability, which is associated with poor breast cancer prognosis.…”

Section: Discussionmentioning

confidence: 99%

Whole exome-seq and RNA-seq data reveal unique neoantigen profiles in Kenyan breast cancer patients

Wagutu,

Gitau,

Mwangi

et al. 2024

Preprint

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BackgroundThe immune response against tumors relies on distinguishing between self and non-self, the basis of cancer immunotherapy. Neoantigens from somatic mutations are central to many immunotherapeutic strategies and understanding their landscape in breast cancer is crucial for targeted interventions. We aimed to profile neoantigens in Kenyan breast cancer patients using genomic DNA and total RNA from paired tumor and adjacent non-cancerous tissue samples of 23 patients.MethodsWe sequenced the genome-wide exome (WES) and RNA, from which somatic mutations were identified and their expression quantified, respectively. Neoantigen prediction focused on human leukocyte antigens (HLA) crucial to cancer, HLA type I. HLA alleles were predicted from WES data covering the adjacent non-cancerous tissue samples, identifying four alleles that were present in at least 50% of the patients. Neoantigens were deemed potentially immunogenic if their predicted median IC50 binding scores were ≤500nM and were expressed [transcripts per million (TPM) >1] in tumor samples.ResultsAn average of 1465 neoantigens covering 10260 genes had ≤500nM median IC50 binding score and >1 TPM in the 23 patients and their presence significantly correlated with the somatic mutations (R2=0.570,P=0.001). Assessing 58 genes reported in the catalog of somatic mutations in cancer (COSMIC, v99) to be commonly mutated in breast cancer, 44 (76%) produced >2 neoantigens among the 23 patients, with a mean of 10.5 ranging from 2 to 93. For the 44 genes, a total of 477 putative neoantigens were identified, predominantly derived from missense mutations (88%), indels (6%), and frameshift mutations (6%). Notably, 78% of the putative breast cancer neoantigens were patient-specific. HLA-C*06:01 allele was associated with the majority of neoantigens (194), followed by HLA-A*30:01 (131), HLA-A*02:01 (103), and HLA-B*58:01 (49). Among the genes of interest that produced putative neoantigens wereMUC17,TTN,MUC16,AKAP9,NEB,RP1L1,CDH23,PCDHB10,BRCA2,TP53,TG, andRB1.ConclusionsThe unique neoantigen profiles in our patient group highlight the potential of immunotherapy in personalized breast cancer treatment as well as potential biomarkers for prognosis. The unique mutations producing these neoantigens, compared to other populations, provide an opportunity for validation in a much larger sample cohort.

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MUC17 mutations and methylation are associated with poor prognosis in adult-type diffuse glioma patients

Cited by 9 publications

References 87 publications

Genomic characterization and risk stratification of esophageal squamous dysplasia

Genomic characterization and risk stratification of esophageal squamous dysplasia

Profiling the molecular and clinical landscape of glioblastoma utilizing the Oncology Research Information Exchange Network brain cancer database

Whole exome-seq and RNA-seq data reveal unique neoantigen profiles in Kenyan breast cancer patients

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