scholarly journals Nanopore sequencing reveals TACC2 locus complexity and diversity of isoforms transcribed from an intronic promoter

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yosuke Ito ◽  
Yasuhisa Terao ◽  
Shohei Noma ◽  
Michihira Tagami ◽  
Emiko Yoshida ◽  
...  

AbstractGene expression is controlled at the transcriptional and post-transcriptional levels. The TACC2 gene was known to be associated with tumors but the control of its expression is unclear. We have reported that activity of the intronic promoter p10 of TACC2 in primary lesion of endometrial cancer is indicative of lymph node metastasis among a low-risk patient group. Here, we analyze the intronic promoter derived isoforms in JHUEM-1 endometrial cancer cells, and primary tissues of endometrial cancers and normal endometrium. Full-length cDNA amplicons are produced by long-range PCR and subjected to nanopore sequencing followed by computational error correction. We identify 16 stable, 4 variable, and 9 rare exons including 3 novel exons validated independently. All variable and rare exons reside N-terminally of the TACC domain and contribute to isoform variety. We found 240 isoforms as high-confidence, supported by more than 20 reads. The large number of isoforms produced from one minor promoter indicates the post-transcriptional complexity coupled with transcription at the TACC2 locus in cancer and normal cells.

2021 ◽  
Author(s):  
Shahan Mamoor

Gynecologic cancers including cancers of the endometrium are a clinical problem (1-4). We mined published microarray data (5, 6) to discover genes associated with endometrial cancers by comparing transcriptomes of the normal endometrium and endometrial tumors from humans. We identified cytoskeleton associated protein 2, encoded by CKAP2, as among the most differentially expressed genes, transcriptome-wide, in cancers of the endometrium. CKAP2 was expressed at significantly higher levels in endometrial tumor tissues as compared to the endometrium. Importantly, in human endometrial cancer, primary tumor expression of CKAP2 was correlated with recurrence-free survival in white patients with high and low mutational burden. CKAP2 may be a molecule of interest in understanding the etiology or progression of human endometrial cancer.


2021 ◽  
Author(s):  
Shahan Mamoor

Gynecologic cancers including cancers of the endometrium are a clinical problem (1-4). We mined published microarray data (5, 6) to discover genes associated with endometrial cancers by comparing transcriptomes of the normal endometrium and endometrial tumors from humans. We identified the insulin degrading enzyme, encoded by IDE, as among the most differentially expressed genes, transcriptome-wide, in cancers of the endometrium. IDE was expressed at significantly higher levels in endometrial tumor tissues as compared to the endometrium. Importantly, primary tumor expression of IDE was correlated with overall survival in patients with endometrial cancer. IDE may be a molecule of interest in understanding the etiology or progression of human endometrial cancer.


2021 ◽  
Author(s):  
Shahan Mamoor

Gynecologic cancers including cancers of the endometrium are a clinical problem (1-4). We mined published microarray data (5, 6) to discover genes associated with endometrial cancers by comparing transcriptomes of the normal endometrium and endometrial tumors from humans. We identified structural maintenance of chromosomes 4, encoded by SMC4, as among the most differentially expressed genes, transcriptome-wide, in cancers of the endometrium. SMC4 was expressed at significantly higher levels in endometrial tumor tissues as compared to the endometrium. Importantly, primary tumor expression of SMC4 was correlated with overall survival in patients with endometrial cancer. SMC4 may be a molecule of interest in understanding the etiology or progression of human endometrial cancer.


2021 ◽  
Author(s):  
Shahan Mamoor

Gynecologic cancers including cancers of the endometrium are a clinical problem (1-4). We mined published microarray data (5, 6) to discover genes associated with endometrial cancers by comparing transcriptomes of the normal endometrium and endometrial tumors from humans. We identified ZW10 interacting kinetochore protein, encoded by ZWINT, as among the most differentially expressed genes, transcriptome-wide, in cancers of the endometrium. ZWINT was expressed at significantly higher levels in endometrial tumor tissues as compared to the endometrium. Importantly, primary tumor expression of ZWINT was correlated with overall survival in patients with endometrial cancer. ZWINT may be a molecule of interest in understanding the etiology and/or progression of human endometrial cancer.


2021 ◽  
Author(s):  
Shahan Mamoor

Gynecologic cancers including cancers of the endometrium are a clinical problem (1, 2, 3, 4). We mined published microarray data (5, 6) to discover genes associated with endometrial cancers by comparing transcriptomes of the normal endometrium and endometrial tumors from humans. We identified the cell cycle component cyclin B1, encoded by CCNB1, as among the most differentially expressed genes, transcriptome-wide, in cancers of the endometrium. CCNB1 was expressed at significantly higher levels in endometrial tumor tissues as compared to the endometrium. Importantly, high primary tumor expression of CCNB1 was correlated with worse overall survival in patients with endometrial cancer. Together, the data reveal over-expression of CCNB1 in human endometrial cancer and describe specific activation of the cell cycle in cancers of the endometrium.


2021 ◽  
Author(s):  
Shahan Mamoor

Gynecologic cancers including cancers of the endometrium are a clinical problem (1, 2, 3, 4). We mined published microarray data (5, 6) to discover genes associated with endometrial cancers by comparing transcriptomes of the normal endometrium and endometrial tumors from humans. We identified the cell cycle component cyclin-dependent kinase 1, encoded by CDK1, as among the most differentially expressed genes, transcriptome-wide, in cancers of the endometrium. CDK1 was expressed at significantly higher levels in endometrial tumor tissues as compared to the endometrium. Importantly, high primary tumor expression of CDK1 was correlated with worse overall survival in patients with endometrial cancer. Together, the data reveal over-expression of CDK1 in human endometrial cancer and describe specific activation of the cell cycle in cancers of the endometrium.


2021 ◽  
Author(s):  
Shahan Mamoor

Gynecologic cancers including cancers of the endometrium are a clinical problem (1-4). We mined published microarray data (5, 6) to discover genes associated with endometrial cancers by comparing transcriptomes of the normal endometrium and endometrial tumors from humans. We identified tubulin beta 4B class IVb, encoded by TUBB4B, as among the most differentially expressed genes, transcriptome-wide, in cancers of the endometrium. TUBB4B was expressed at significantly higher levels in endometrial tumor tissues as compared to the endometrium. Importantly, primary tumor expression of TUBB4B was correlated with overall survival in patients with endometrial cancer. TUBB4B may be a molecule of interest in understanding the etiology or progression of human endometrial cancer.


2021 ◽  
Author(s):  
Shahan Mamoor

Gynecologic cancers including cancers of the endometrium are a clinical problem (1-4). We mined published microarray data (5, 6) to discover genes associated with endometrial cancers by comparing transcriptomes of the normal endometrium and endometrial tumors from humans. We identified adenosine kinase, encoded by ADK, as among the most differentially expressed genes, transcriptome-wide, in cancers of the endometrium. ADK was expressed at significantly higher levels in endometrial tumor tissues as compared to the endometrium. Importantly, primary tumor expression of ADK was correlated with overall survival in patients with endometrial cancer. ADK may be a molecule of interest in understanding the etiology or progression of human endometrial cancer.


Author(s):  
Anu Sarah Easo ◽  
Rajeev Anand ◽  
Mini Issac

Background: To determine whether diffusion-weighted imaging (DWI) with measurement of apparent diffusion coefficient (ADC) will help in differentiating endometrial cancer from normal endometrium and to determine whether the grades of endometrial cancer will show significant difference in ADC values.Methods: This is a retrospective study done in MOSC medical college hospital Kolencherry. on patients on whom preoperative MRI was done before hysterectomy. Cases from July 2017 to March 2021 were included. Study cases included 40 females with pathologically confirmed endometrial cancer and 30 females with pathologically proven normal endometrium in cases of uterine leiomyoma and cervical cancer. The exclusion criteria for the study were patients with endometrial cancer in whom surgery was not done within 2 weeks of MRI, patients who were treated with chemotherapy or radiotherapy before surgery, patients who had hydrometra or pyometra.Results: The mean ADC value (10−3 mm2/second) of endometrial cancer was 0.77±0.04, which was significantly lower (p<0.05) than that of normal endometrium (1.323±0.05). The ADC values of different grades of endometrial cancers did not show any statistically significant difference (p>0.05).Conclusions: Our study showed that ADC measurement can differentiate between normal endometrium and endometrial cancer. The ADC values of different grades of endometrial cancers did not show any statistically significant difference.  


2021 ◽  
Author(s):  
Shahan Mamoor

Gynecologic cancers including cancers of the endometrium are a clinical problem (1-4). We mined published microarray data (5, 6) to discover genes associated with endometrial cancers by comparing transcriptomes of the normal endometrium and endometrial tumors from humans. We identified cell division cycle 20, encoded by CDC20, as among the most differentially expressed genes, transcriptome-wide, in cancers of the endometrium. CDC20 was expressed at significantly higher levels in endometrial tumor tissues as compared to the endometrium. Importantly, high primary tumor expression of CDC20 was correlated with worse overall survival in white endometrial cancer patients with high mutational burden. The data allude to activation of the endometrial cell cycle in patients with endometrial cancer.


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