Dear Label_Name,

Greetings! I hope you are well.

I am writing on behalf of an international publishing house, Science and Education Publishing, USA (http://www.sciepub.com).

Science and Education Publishing (SciEP) is a multidisciplinary open access publisher of Journals covering the fields of Science, Technology and Medicine. All SciEP publications are subject to high-quality peer review, editorial and production processes and are freely available online.

Welcome to the April, 2013 edition of SciEP newsletter, providing monthly summaries of articles on science & education related topics of interest to scientist and professionals. The mission of our journals is to provide an open access forum for publishing new findings on issues pertinent to scientific and academic field. We also invite you to submit original research papers, review articles, short reports, or case studies are considered for publication in our Multidisciplinary Journals.

American Journal of Public Health Research
DOI: 10.12691/ajphr-1-1-3

The Implementation of a Tele-Homecare System with Service Oriented Architecture and HL7 Message Transmission Standard
Ching-Sung Wang

American Journal of Medical and Biological Research
DOI: 10.12691/ajmbr-1-1-2

The Influence of Ethanol on Pyruvate Kinases Activity in Vivo, in Vitro, in Silico
Lelevich Sergey Vladimirovich, Khrustalev Vladislav Victorovich, Barkovsky Eugene Victorovich, Shedogubova Tatyana Aleksandrovna

American Journal of Medical Sciences and Medicine
DOI: 10.12691/ajmsm-1-1-1

Clinical and Histological Features in Wegener Granulomatosis
Li Cavoli Gioacchino, Passantino Rita, Bono Luisa, Tortorici Calogera, Ferrantelli Angelo, Giammarresi Carlo, Rotolo Ugo

American Journal of Infectious Diseases and Microbiology
DOI: 10.12691/ajidm-1-1-2

The Curse of Lymphatic Filariasis: Would the Continual Use of Diethylcarbamazine Eliminate this Scourge in Papua New Guinea?
Anne Lanham, Lillian Mwanri

We have released issues of some journals on February 2013.
American Journal of Public Health Research
American Journal of Medical Sciences and Medicine
American Journal of Medical and Biological Research
American Journal of Pharmacological Sciences
American Journal of Clinical Medicine Research
American Journal of Nursing Research
American Journal of Cancer Prevention
American Journal of Medicine Studies
American Journal of Infectious Diseases and Microbiology
American Journal of Cardiovascular Disease Research
American Journal of Biomedical Research
American Journal of Mechanical Engineering
American Journal of Microbiological Research
Journal of Preventive Medicine
American Journal of Food and Nutrition
American Journal of Hypertension Research
American Journal of Sports Science and Medicine
Journal of Cancer Research and Treatment
American Journal of Zoological Research
Journal of Biomedical Engineering and Technology
American Journal of Microbiological Research
Biomedical Science and Engineering

We are pleased to announce that submissions are now being accepted for peer review for all the journals across all our subject areas in SciEP.

Please submit your manuscript via our online submission system:
http://www.sciepub.com/author/signin

To unsubscribe from our mailing list, please click on the following link: unsubscribe

I am looking forward to hearing from you.

Kind regards,

David Rain
Email:join@sciepub.com
Science and Education Publishing (http://www.sciepub.com)

Oncogenomics of Mesothelioma in Humans

Manop Pitukpakorn, Somchai Bovornkitti*

Faculty of Medicine Siriraj Hospital, Mahidol University

Abstract:

Keywords:

Citation: Manop Pitukpakorn, Somchai Bovornkitti, Oncogenomics of Mesothelioma in Humans. American Journal of Public Health Research, 6 (2). 63-64. January 2018. doi:10.12691/ajphr-6-2-8

Beginning in 1990, the Human Genome Project brought about a significant breakthrough in medical genetics and application of genetic knowledge in common diseases. It has revolutionized the traditional medical concept that genetics is involved only in extremely rare inherited diseases, to the new concept that genetic factors significantly contribute to the mechanism and progression of most diseases, as well as the response and side effects of the treatment. [1] Cancer is the best example to demonstrate the benefits of genetic knowledge. It is universally accepted that cancer is a genetic disorder that results in abnormal cell growth and invasiveness with the potential to spread to other parts of the body. Better understanding of cancer genetics leads to new types of cancer diagnostic tests and several novel drugs which are designed to target specific genetic abnormalities in cancer. Many patients who are suffering from various cancers, such as leukemia, breast cancer and lung cancer, are now having better treatment outcomes, longer life expectancy and suffering less adverse effects from treatment with those targeted therapies.

In addition to many discoveries on the genetic factors of more common diseases, innovation in molecular genetic technology also gives rise to revolutionary high throughput genome sequencing. From the era of capillary electrophoresis-based sequencing, it took 11 years and cost nearly $3 billion to complete the entire human genome sequence. The new technology, called “next generation sequencing (NGS),” makes large-scale genome sequencing possible. It currently takes less than two weeks and costs less than $2,000 to accomplish the sequencing of one human genome. The unprecedented throughput, speed and cost of sequencing enables researchers to investigate the genetic contribution of cancer and implement this NGS technology in real-world medical practice at a level never before possible.

Similar to the Human Genome Project, the United States National Institutes of Health together with several leading research institutes created the Cancer Genome Atlas in 2005 with the aim of achieving large-scale and comprehensive tumor genome sequencing of various cancers. We currently see widespread use of NGS in cancer research to discover genetic alterations in each cancer, to study disease mechanisms at the molecular level, to identify potential treatment targets, to predict the response to medical treatment and to use this technology to tailor the appropriate treatment for each patient.

Mesothelioma Tumor Genome

Mesothelioma is a cancer that arises from mesothelial cells. Though there are various affected organs, including the peritoneum and pericardium, pleural mesothelioma accounts for more than 90 percent of cases. It is a rare cancer with estimated incidence of about 10-20 cases per million. [2] Approximately 80 percent of pleural mesothelioma cases are associated with asbestos exposure. The disease carries a dismal prognosis since the majority of cases are diagnosed at advanced stages. The median overall survival ranges from 8 to 36 months. Current drug regimens are mostly ineffective. Thus, understanding the genetic alterations of mesothelioma is critical for successful development of diagnostic and therapeutic strategies.

The largest and most systematic investigation on mesothelioma tumor genetic alteration has been published recently. [3] The cohort consisted of 216 mesothelioma cases. The comprehensive study revealed several crucial findings on mesothelioma. The majority of the mutations (approximately 85 percent) were novel. None of the tumor samples carried germline variants in known cancer-associated genes. The average mutation burden was also low (24 +/- 11 protein-coding alterations per sample) unlike other solid tumors, especially tumors that were slow-growing and were associated with environmental exposure, such as lung cancer or colorectal cancer.

The mutation landscape of mesothelioma is more distinct than other cancers. Tumor suppressors BAP1 and NF2 were mutated in 23 percent and 19 percent of the samples, respectively. In contrast, TP53 was mutated in only 8 percent. Other significant alteration includes autophagy kinase ULK2, a target of mammalian target of rapamycin (mTOR) negative regulation implicated in glioma development, which was mutated in 1.5 percent and SETD2, encoding a member of the SET domain family containing histone methyltransferase, which was mutated in 8 percent of the samples. Overall, the majority of altered genes found in mesothelioma are involved in four cell signaling pathways; the Hippo (NF2, LATS1, MST1), mTOR (ULK2, TSC1, TSC2), apoptosis (TP53, CDKN2A, CDKN2B), and histone modification (SETD2, SETDB1, SETD5).

In conclusion, cancer arises from genetic dysfunction leading to out-of-control cell growth, causing tumor growth and spreading. Since each patient has a unique set of gene mutations driving cancer, there are multiple targets in each patient that may need to be hit. This is where tumor profiling is useful.

Analyzing an individual patient’s tumor is necessary to determine what combination of drugs will work best. With this approach also comes greater potential to decrease toxic side effects. Targeted drugs would give the ability to customize treatments for the patient. Further insight from mesothelioma genome and cellular pathways would enable physicians to move treatment from a broad-based approach – using radiation, surgery, and chemotherapy-to a more targeted technique in the future, which would that interfere with essential cell functions to kill cancer cells.

References

[1]   | Green, E.D., Watson, J.D., Collins, F.S. Human Genome Project: Twenty-five years of big biology. Nature, 526 (7571): 29-31. 2015.
[2]   | Robinson, B.M. Malignant pleural mesothelioma: an epidemiological perspective. Annals of Cardiothoracic Surgery, 2; 1(4): 491-496. 2012.
[3]   | Bueno, R., Stawiski, E.W., Goldstein, L.D., Durinck, S., De Rienzo, A., Modrusen, Z., et al. Comprehensive genomic analysis of malignant pleural mesothelioma identifies recurrent mutations, gene fusions and splicing alterations. Nature Genetics, 48(4): 407-416. 2016.