Alternative Splicing in Prostate and Breast Cancer

Watson, Patricia M.; Watson, Dennis K.

doi:10.2174/1874079001003010062

Cited by 5 publications

(5 citation statements)

References 118 publications

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“…For example, it was found that over one third of exons can be skipped (~38%) (Ast, 2004 ; Sugnet et al, 2004 ). “Pathological” exon skipping is commonly seen in diseases with multiple disrupted alternative splicing events, especially in cancer (Watson and Watson, 2010 ).…”

Section: Resultsmentioning

confidence: 99%

“…There are many practical uses for understanding the alternative RNA splicing code. For example, many diseases, including cancer, have mutations that cause changes in alternative RNA splicing that contribute to pathogenesis (Watson and Watson, 2010 ). It is estimated that at least 15–50% of mutations that cause human diseases affect splice-site selection (Wang and Cooper, 2007 ; Singh and Cooper, 2012 ).…”

Section: Resultsmentioning

confidence: 99%

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A Bioinformatics-Based Alternative mRNA Splicing Code that May Explain Some Disease Mutations Is Conserved in Animals

et al. 2017

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Deep sequencing of cDNAs made from spliced mRNAs indicates that most coding genes in many animals and plants have pre-mRNA transcripts that are alternatively spliced. In pre-mRNAs, in addition to invariant exons that are present in almost all mature mRNA products, there are at least 6 additional types of exons, such as exons from alternative promoters or with alternative polyA sites, mutually exclusive exons, skipped exons, or exons with alternative 5′ or 3′ splice sites. Our bioinformatics-based hypothesis is that, in analogy to the genetic code, there is an “alternative-splicing code” in introns and flanking exon sequences, analogous to the genetic code, that directs alternative splicing of many of the 36 types of introns. In humans, we identified 42 different consensus sequences that are each present in at least 100 human introns. 37 of the 42 top consensus sequences are significantly enriched or depleted in at least one of the 36 types of introns. We further supported our hypothesis by showing that 96 out of 96 analyzed human disease mutations that affect RNA splicing, and change alternative splicing from one class to another, can be partially explained by a mutation altering a consensus sequence from one type of intron to that of another type of intron. Some of the alternative splicing consensus sequences, and presumably their small-RNA or protein targets, are evolutionarily conserved from 50 plant to animal species. We also noticed the set of introns within a gene usually share the same splicing codes, thus arguing that one sub-type of splicesosome might process all (or most) of the introns in a given gene. Our work sheds new light on a possible mechanism for generating the tremendous diversity in protein structure by alternative splicing of pre-mRNAs.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

A Bioinformatics-Based Alternative mRNA Splicing Code that May Explain Some Disease Mutations Is Conserved in Animals

et al. 2017

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“…We also observed the differential expression of LSM family genes (LSM2, LSM3, LSM4, LSM5 and LSM7), a family of RNA‐binding proteins found in virtually every cellular organism. Multiple studies demonstrated that alterative splicing patterns are altered during cancer progression, including prostate cancer (Watson & Watson, ). Genes that play a role in DNA replication are members of small nuclear ribonucleoprotein polypeptides (SNRPA1, SNRPB, SNRPD1, SNRPE, SNRPF and SNRPG).…”

Section: Discussionmentioning

confidence: 99%

A computational bioinformatics analysis of gene expression identifies candidate agents for prostate cancer

Geng

et al. 2013

Andrologia

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Prostate cancer is the second most frequently diagnosed cancer and the sixth leading cause of cancer death in males worldwide. Although great progress has been made, the molecular mechanisms of prostate cancer are far from being fully understood and treatment of this disease remains palliative. In this study, we sought to explore the molecular mechanism of prostate cancer and then identify biologically active small molecules capable of targeting prostate cancer using a computational bioinformatics analysis of gene expression. A total of 3068 genes, involved in cell communication, development, localisation and cell proliferation, were differentially expressed in prostate cancer samples compared with normal controls. Pathways associated with signal transduction, immune response and tumorigenesis were dysfunctional. Further, we identified a group of small molecules capable of reversing prostate cancer. These candidate agents may provide the groundwork for a combination therapy approach for prostate cancer. However, further evaluation for their potential use in the treatment of prostate cancer is still needed.

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“…In addition to nonsynonymous mutations arising from single nucleotide substitutions, several splice variants specific to breast cancer have been reported 134,135. Interestingly, breast cancer-specific alternative splicing is not restricted to splicing defects resulting in loss of protein functions, and may also include modifications that generate proteins with new functions 134…”

Section: Genetic Alterations In Breast Cancermentioning

confidence: 99%

“…Different ESR2 (estrogen receptor β) splice variants have been identified and studies on the function of some of these suggested that they might act as a dominant negative receptor in the estrogen receptor α and β pathways 135,139…”

Section: Genetic Alterations In Breast Cancermentioning

confidence: 99%

Inherited and acquired alterations in development of breast cancer

Rizzolo¹,

Silvestri²,

Falchetti³

et al. 2011

TACG

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Breast cancer is the most common cancer among women, accounting for about 30% of all cancers. In contrast, breast cancer is a rare disease in men, accounting for less than 1% of all cancers. Up to 10% of all breast cancers are hereditary forms, caused by inherited germ-line mutations in “high-penetrance,” “moderate-penetrance,” and “low-penetrance” breast cancer susceptibility genes. The remaining 90% of breast cancers are due to acquired somatic genetic and epigenetic alterations. A heterogeneous set of somatic alterations, including mutations and gene amplification, are reported to be involved in the etiology of breast cancer. Promoter hypermethylation of genes involved in DNA repair and hormone-mediated cell signaling, as well as altered expression of micro RNAs predicted to regulate key breast cancer genes, play an equally important role as genetic factors in development of breast cancer. Elucidation of the inherited and acquired genetic and epigenetic alterations involved in breast cancer may not only clarify molecular pathways involved in the development and progression of breast cancer itself, but may also have an important clinical and therapeutic impact on improving the management of patients with the disease.

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Alternative Splicing in Prostate and Breast Cancer

Cited by 5 publications

References 118 publications

A Bioinformatics-Based Alternative mRNA Splicing Code that May Explain Some Disease Mutations Is Conserved in Animals

A Bioinformatics-Based Alternative mRNA Splicing Code that May Explain Some Disease Mutations Is Conserved in Animals

A computational bioinformatics analysis of gene expression identifies candidate agents for prostate cancer

Inherited and acquired alterations in development of breast cancer

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