The early manifestation, tumor-specific occurrence and prognostic significance of TGFBR2 aberrant splicing in oral carcinoma

Sivadas, V. P.; Gulati, Saakshi; Varghese, Bipin T.; Balan, Anita; Kannan, S.

doi:10.1016/j.yexcr.2014.05.004

Cited by 11 publications

(6 citation statements)

References 25 publications

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“…(Figure 2G). Intronic variants within TGFβR2 gene have already been reported in oral carcinoma as a result of aberrant splicing [57]. Such might be the case for the validated intronic mutations in the present study.…”

Section: Discussionsupporting

confidence: 59%

Targeted exome sequencing reveals distinct pathogenic variants in Iranians with colorectal cancer

et al. 2016

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PURPOSENext Generation Sequencing (NGS) is currently used to establish mutational profiles in many multigene diseases such as colorectal cancer (CRC), which is on the rise in many parts of the developing World including, Iran. Little is known about its genetic hallmarks in these populations.AIMTo identify variants in 15 CRC-associated genes in patients of Iranian descent.RESULTSThere were 51 validated variants distributed on 12 genes: 22% MSH3 (n = 11/51), 10% MSH6 (n = 5/51), 8% AMER1 (n = 4/51), 20% APC (n = 10/51), 2% BRAF (n = 1/51), 2% KRAS (n = 1/51), 12% PIK3CA (n = 6/51), 8% TGFβR2A (n = 4/51), 2% SMAD4 (n = 1/51), 4% SOX9 (n = 2/51), 6% TCF7L2 (n = 3/51), and 6% TP53 (n = 3/51). Most known and distinct variants were in mismatch repair genes (MMR, 32%) and APC (20%). Among oncogenes, PIK3CA was the top target (12%).MATERIALS AND METHODSCRC specimens from 63 Shirazi patients were used to establish the variant' profile on an Ion Torrent platform by targeted exome sequencing. To rule-out technical artifacts, the variants were validated in 13 of these samples using an Illumina NGS platform. Validated variants were annotated and compared to variants from publically available databases. An in-silico functional analysis was performed. MSI status of the analyzed samples was established.CONCLUSIONThese results illustrate for the first time CRC mutational profile in Iranian patients. MSH3, MSH6, APC and PIK3CA genes seem to play a bigger role in the path to cancer in this population. These findings will potentially lead to informed genetic diagnosis protocol and targeted therapeutic strategies.

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Section: Discussionsupporting

confidence: 59%

Targeted exome sequencing reveals distinct pathogenic variants in Iranians with colorectal cancer

et al. 2016

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“…FIR is predicted to possess two long IDPRs (residues 1–126 and 300–500), with the N-terminal disordered domain being missing in AS isoforms. The high prevalence of AS in transforming growth factor beta receptor 2 (TGFBR2) has been recently reported in oral squamous cell carcinoma (OSCC) and in potentially malignant oral disorders (PMDs), with almost no such event detected in normal tissues (Sivadas et al, 2014 ). The AS of TGFBR2 occurred at the non-canonical splice sites and resulted in a selective exclusion of TGFBR2 mRNA sequences that code for TGFBR2 regions involved in tumor suppressive interactions such as ATM, CLK2, and CDC2, whereas the TGFBR2 sites related to the tumor promoting interactions such as interactions with MAPK1, PDK1, and PRKCZ were maintained in these aberrant transcripts (Sivadas et al, 2014 ).…”

Section: Wrecked Regulation Of Idps and Diseasementioning

confidence: 99%

Wrecked regulation of intrinsically disordered proteins in diseases: pathogenicity of deregulated regulators

Uversky

2014

Front. Mol. Biosci.

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Biologically active proteins without stable tertiary structure are common in all known proteomes. Functions of these intrinsically disordered proteins (IDPs) are typically related to regulation, signaling, and control. Cellular levels of these important regulators are tightly regulated by a variety mechanisms ranging from firmly controlled expression to precisely targeted degradation. Functions of IDPs are controlled by binding to specific partners, alternative splicing, and posttranslational modifications among other means. In the norm, right amounts of precisely activated IDPs have to be present in right time at right places. Wrecked regulation brings havoc to the ordered world of disordered proteins, leading to protein misfolding, misidentification, and missignaling that give rise to numerous human diseases, such as cancer, cardiovascular disease, neurodegenerative diseases, and diabetes. Among factors inducing pathogenic transformations of IDPs are various cellular mechanisms, such as chromosomal translocations, damaged splicing, altered expression, frustrated posttranslational modifications, aberrant proteolytic degradation, and defective trafficking. This review presents some of the aspects of deregulated regulation of IDPs leading to human diseases.

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“…Impact of dohra on human health :Consumption of dohra leads to oral submucous fibrosis which is a commonly known condition in tobacco chewers as well 5 12 . It decreases the salivary secretion (xerostomia), causes dental problems (stained teeth, periodontitis), digestive system problems and intestinal cancer 13 .…”

Section: Resultsmentioning

confidence: 99%

Dohra- a mixture of potent carcinogens

Sharma¹,

Nandan²,

Shukla³

et al. 2018

Indian J Med Res

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Background & objectives:Dohra is a areca nut preparation used with or without tobacco in a few of the areas of Uttar Pradesh (UP), India. There is evidence that it causes potentially malignant disorders and oral cancer. This study was undertaken to provide information on dohra by searching through literature and also through a survey in three areas of Uttar Pradesh (UP), India.Methods:The information on dohra was collected through literature search, study tour to different areas of UP, where group discussions with dohra vendors and with community members of different age group were done to obtain information.Results:Dohra was prepared by the users for their personal use or prepared by small-scale industry for sale. It was available mostly in betel shops or any other store/kiosks and was also available in special dohra shops. Dohra was available in both dry and wet form. Its common constituents were areca nut, catechu (Acacia catechu), edible lime, peppermint (Mentha piperita), cardamom (Elettaria cardamomum) and some flavoring agents. Dohra was consumed as such or with tobacco.Interpretation & conclusions:Different varieties of Dohra were available such as sukha dohra, sukha mulethi dohra and geela dohra. Different processing methods for producing dohra existed. As dohra increases the risk of cancer, it needs to be banned or it should be sold in packets with the details of its constituents and also statutory warning about its adverse health effects.

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The early manifestation, tumor-specific occurrence and prognostic significance of TGFBR2 aberrant splicing in oral carcinoma

Cited by 11 publications

References 25 publications

Targeted exome sequencing reveals distinct pathogenic variants in Iranians with colorectal cancer

Targeted exome sequencing reveals distinct pathogenic variants in Iranians with colorectal cancer

Wrecked regulation of intrinsically disordered proteins in diseases: pathogenicity of deregulated regulators

Dohra- a mixture of potent carcinogens

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