Features | Partner Sites | Information | LinkXpress
Sign In
PZ HTL SA
GLOBETECH PUBLISHING
GLOBETECH PUBLISHING

Whole Exome Sequencing of Small Intestine Neuroendocrine Tumors May Lead to Development of Personalized Treatment

By BiotechDaily International staff writers
Posted on 30 May 2013
Image: First author Dr. Michaela S. Banck (Photo courtesy of the Mayo Clinic).
Image: First author Dr. Michaela S. Banck (Photo courtesy of the Mayo Clinic).
Whole exome sequencing of small intestine neuroendocrine tumors, the most common malignancy of the small bowel, revealed genomic alterations that might be susceptible to chemotherapy in 72% of the patients studied.

The exome is the part of the genome formed by exons, nucleotide sequences encoded by a gene that remain present within the final mature RNA product of that gene after introns have been removed by RNA splicing. The term exon refers to both the DNA sequence within a gene and to the corresponding sequence in RNA transcripts. The exome of the human genome consists of roughly 180,000 exons constituting about 1% of the total genome, or about 30 megabases of DNA. Though comprising a very small fraction of the genome, mutations in the exome are thought to harbor 85% of disease-causing mutations.

Investigators at the Mayo Clinic (Rochester, MN, USA) analyzed the exomes of small intestine neuroendocrine tumors from 48 patients, along with normal tissue from those same 48 patients. They employed massively parallel, or “nextgen,” DNA sequencing, which facilitates the collection of comprehensive, genome-wide, unbiased datasets providing a common data framework for comparing results across different tumor types and gene sets. This technique provides the most comprehensive technology to date to explore the potential of genomics for individualizing cancer treatment within a tumor type.

Data obtained from analysis of the 96 whole exome sequences was published in the May 15, 2013, online edition of the Journal of Clinical Investigation. The findings revealed that small intestine neuroendocrine tumors samples carried low numbers of point mutations and characteristic recurrent patterns of gene duplications and losses. Candidate therapeutically relevant alterations were found in 35 of the 48 patients, including SRC, SMAD family genes, AURKA, EGFR, HSP90, and PDGFR. Mutually exclusive amplification of the serine-threonine protein kinases AKT1 or AKT2 was the most common event in 16 patients who displayed alterations of PI3K/AKT/mTOR signaling. AKT1 (v-akt murine thymoma viral oncogene homolog 1) is a component of the PI3K/AKT/mTOR pathway, and mutations in AKT1 have been implicated in breast, colorectal, and lung cancers,

“This is a very important step in achieving targeted therapies and individualized treatment approaches for patients with small bowel carcinoids,” said first author Dr. Michaela Banck, an oncologist at the Mayo Clinic. “Genomic analysis of the individual patient’s tumors will help us identify new drugs that are targeted to the individual’s disease.”

Related Links:
Mayo Clinic



Channels

Drug Discovery

view channel
Image: Chitosan is derived from the shells of shrimp and other sea crustaceans, including Alaskan pink shrimp, pictured here (Photo courtesy of NOAA - [US] National Oceanic and Atmospheric Administration).

Chitosan Treatment Clears the Way for Antibiotics to Eliminate Recurrent Urinary Tract Infections

Recurrent urinary tract infection was successfully resolved in a mouse model by treatment with the exfoliant chitosan followed by a round of antibiotics. Bacterial urinary tract infection (UTI), most... Read more

Biochemistry

view channel

Mitochondrial Cause of Aging Can Be Reversed

Researchers have found a cause of aging in lab animals that can be reversed, possibly providing an avenue for new treatments for age-related diseases including type 2 diabetes, cancer, muscle wasting, and inflammatory diseases. The researchers plan to begin human trials late 2014. The study, which was published December... Read more

Therapeutics

view channel

Cytokine Identified That Causes Mucositis in Cancer Therapy Patients

The action of the cytokine interleukin 1-beta (IL-1beta) has been found to underlie the onset of mucositis, a common, severe side effect of chemotherapy and irradiation of cancer patients. Mucositis occurs as a result of cell death in reaction to chemo- or radiotherapy. The mucosal lining of the mouth becomes thin, may... Read more

Business

view channel

Analytical Sciences Trade Fair Declared a Rousing Success

Organizers of this year's 24th "analytica" biosciences trade fair have reported significant increases in both the number of visitors and exhibitors compared to the 2012 event. The analytica trade fair for laboratory technology, analysis, and biotechnology has been held at the Munich (Germany) Trade Fair Center every... Read more
 
Copyright © 2000-2014 Globetech Media. All rights reserved.