Molecular alterations and clinical relevance in cervical carcinoma and precursors (Review)

Abstract The methylation of N6 adenosine (m6A) plays a critical role in diverse biological processes. However, knowledge regarding the reconstitution of m6A across cancer types is still lacking. Here, we systematically analyzed the molecular alterations and clinical relevance of m6A regulators across > 10,000 subjects representing 33 cancer types. We found that there are widespread genetic alterations to m6A regulators, and that their expression levels are significantly correlated with the activity of cancer hallmark-related pathways. Moreover, m6A regulators were found to be potentially useful for prognostic stratification, and we identified IGF2BP3 as a potential oncogene across multiple cancer types. Our results provide a valuable resource that will guide both mechanistic and therapeutic analyses of the role of m6A regulators in cancer.

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Analysis of molecular alterations in chromosome 8 associated with the development of uterine cervical carcinoma of Indian patients

Gynecologic Oncology ◽

10.1016/j.ygyno.2004.07.036 ◽

2004 ◽

Vol 95 (2) ◽

pp. 352-362 ◽

Cited By ~ 10

Author(s):

N. Bhattacharya ◽

R.K. Singh ◽

S. Mondal ◽

A. Roy ◽

R. Mondal ◽

...

Keyword(s):

Cervical Carcinoma ◽

Chromosome 8 ◽

Uterine Cervical Carcinoma ◽

Molecular Alterations ◽

Indian Patients

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Molecular alterations and clinical relevance in esophageal squamous cell carcinoma

Frontiers of Medicine ◽

10.1007/s11684-013-0286-y ◽

2013 ◽

Vol 7 (4) ◽

pp. 401-410 ◽

Cited By ~ 19

Author(s):

Li Shang ◽

Mingrong Wang

Keyword(s):

Squamous Cell Carcinoma ◽

Esophageal Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Clinical Relevance ◽

Molecular Alterations

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Molecular Characterization and Clinical Relevance of ALDH2 in Human Cancers

Frontiers in Medicine ◽

10.3389/fmed.2021.832605 ◽

2022 ◽

Vol 8 ◽

Author(s):

Bo Ma ◽

Zaoqu Liu ◽

Hui Xu ◽

Long Liu ◽

Tao Huang ◽

...

Keyword(s):

Clinical Relevance ◽

Large Scale ◽

Copy Number Variations ◽

Dna Hypermethylation ◽

Molecular Alterations ◽

Human Cancers ◽

Mutation Burden ◽

Public Data ◽

Precise Diagnosis ◽

Key Enzyme

Background: Aldehyde dehydrogenase 2 (ALDH2) is well-known to be a key enzyme in alcohol metabolism. However, a comprehensive understanding of ALDH2 across human cancers is lacking.Methods: A systematic and comprehensive analysis of the molecular alterations and clinical relevance for ALDH2 in more than 10,000 samples from 33 cancer types was performed. qRT-PCR was performed on 60 cancer and 60 paired nontumor tissues.Results: It was observed that ALDH2 was generally downregulated in most cancers, which was mainly driven by DNA hypermethylation rather than mutations or copy number variations. Besides, ALDH2 was closely related to the inhibition and activation of tumor pathways and a variety of potential targeted agents had been discovered in our research. Last but not least, ALDH2 had the best prediction efficacy in assessing immunotherapeutic response compared with PD-L1, PD-1, CTLA4, CD8, and tumor mutation burden (TMB) in cutaneous melanoma. According to the analysis of large-scale public data and 60 pairs of clinical cancer samples, we found the downregulation of ALDH2 expression tends to suggest the malignant phenotypes and adverse prognosis, which might enhance the precise diagnosis and timely intervention of cancer patients.Conclusion: This study advanced the understanding of ALDH2 across cancers, and provided important insight into chemotherapy, immunotherapy and prognosis of patients with cancer.

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Clinical relevance of miRNA expression in metastatic melanoma

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.9006 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 9006-9006

Author(s):

M. F. Segura ◽

J. Zakrzewski ◽

I. Belitskaya-Levy ◽

A. Gaziel ◽

M. Kushnir ◽

...

Keyword(s):

Soft Tissue ◽

Metastatic Melanoma ◽

Mirna Expression ◽

Clinical Relevance ◽

Misclassification Error ◽

Biological Behavior ◽

Mirna Cluster ◽

Tissue Samples ◽

Molecular Alterations ◽

Formalin Fixed Paraffin Embedded

9006 Background: We recently reported the identification of a specific miRNA cluster frequently overexpressed in melanoma which enhances the metastatic behavior (Segura et al., 2009. PNAS. In press). In this study, we aim to define the clinical relevance of miRNA expression, in particular whether miRNAs can serve as prognostic biomarkers for melanoma patients. Methods: Total RNA was extracted from formalin-fixed paraffin embedded (FFPE) tissue samples from 61 metastatic melanoma specimens (25 lymph node, 16 soft tissue/skin, 13 brain and 7 visceral) accrued by the NYU Interdisciplinary Melanoma Cooperative Group (IMCG). RNA was hybridized into miRNA arrays (miRdicatorTM, Rosetta Genomics, Inc) containing probes for more than 600 miRNA sequences, including all the human miRNAs in the 9.0 version of miRBase. The Significance Analysis of Microarrays (SAM) was used to identify miRNAs significantly associated with survival, and the False Discovery Rate (FDR) approach was used to adjust for multiple comparisons. Results: We identified a signature of 18 miRNAs, whose up-regulation significantly associates with better prognosis (increased overall survival and post-recurrence survival) using the FDR of 0%. Quantitative RT-PCR on the same tissues has verified the array results in 15 out of 15 miRNAs analyzed. Some of these miRNAs were significantly associated with stage at recurrence, while others significantly correlated with the site of metastasis (i.e. visceral, brain, soft-tissue). Using cross-validation, we selected a miRNA signature consisting of 10 of these significant miRNAs with lowest misclassification error in predicting 1.5-year post-recurrence survival. We are currently validating these findings in a separate cohort of metastatic patients. Furthermore, we are investigating whether these ‘protective' miRNAs can be detected in the corresponding primary lesions and thus, whether they already hold prognostic value at early stages of the disease. Conclusions: Our data suggest a role for miRNAs as melanoma biomarkers, and support the development of miRNA- based monitoring assays. These analyses are also expanding our understanding of the molecular alterations underlying melanoma progression, by revealing miRNAs whose down-regulation associates with a more aggressive biological behavior. [Table: see text]

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Actionable Molecular Alterations Are Revealed in Majority of Advanced Non-Small Cell Lung Cancer Patients by Genomic Tumor Profiling at Progression after First Line Treatment

Cancers ◽

10.3390/cancers14010132 ◽

2021 ◽

Vol 14 (1) ◽

pp. 132

Author(s):

Malene Støchkel Frank ◽

Uffe Bodtger ◽

Julie Gehl ◽

Lise Barlebo Ahlborn

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Clinical Relevance ◽

Small Cell ◽

Genomic Profiling ◽

Line Treatment ◽

Small Cell Lung ◽

First Line ◽

Molecular Alterations ◽

First Line Treatment

Background: Genomic profiling in advanced Non-Small Cell Lung cancer (NSCLC) can reveal Actionable Molecular Alterations (AMAs). Our study aims to investigate clinical relevance of re-biopsy after first line treatment, by reporting on acquired and persistent AMAs and potential targeted treatments in a real-time cohort of NSCLC patients. Methods: Patients with advanced NSCLC receiving first-line treatment were prospectively included in an observational study (NCT03512847). Genomic profiling was performed by TruSight Oncology 500 HT gene panel on tumor tissue collected at diagnosis and at time of progression. Results: The 92 patients re-biopsied at progression had received immunotherapy (n = 44), chemotherapy (n = 44), or combination treatment (n = 4). In 87 of these patients (95%), successful genomic profiling was performed at both the diagnostic biopsy and the re-biopsy. In 74 patients (85%), ≥1 AMA were found. The AMAs were acquired in 28%. The most frequent AMAs were observed in TP53 (45%), KRAS (24%), PIK3CA (6%), and FGFR1 (6%). Only five patients (5%) received targeted treatment mainly due to deterioration in performance status. Conclusions: Re-biopsy at progression revealed acquired AMAs in approximately one third of patients, and 85% had at least one AMA with the potential of receiving targeted treatment, thus strengthening the clinical relevance of re-biopsy.

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Selected Abstracts of Recent Research in Stuttering

Perspectives on Fluency and Fluency Disorders ◽

10.1044/ffd9.1.5 ◽

1999 ◽

Vol 9 (1) ◽

pp. 5-6

Author(s):

Carrie Bain ◽

Nan Bernstein Ratner

Keyword(s):

Large Volume ◽

Clinical Relevance

Due to the large volume of fluency-related publications since the last column, we have chosen to highlight those articles of highest potential clinical relevance.

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