alexa Pathogenesis of Sarcomas | Open Access Journals
Diagnostic Pathology: Open Access
Like us on:
Make the best use of Scientific Research and information from our 700+ peer reviewed, Open Access Journals that operates with the help of 50,000+ Editorial Board Members and esteemed reviewers and 1000+ Scientific associations in Medical, Clinical, Pharmaceutical, Engineering, Technology and Management Fields.
Meet Inspiring Speakers and Experts at our 3000+ Global Conferenceseries Events with over 600+ Conferences, 1200+ Symposiums and 1200+ Workshops on
Medical, Pharma, Engineering, Science, Technology and Business

Pathogenesis of Sarcomas

Eleanor Chen*

Department of Pathology, University of Washington, USA

*Corresponding Author:
Eleanor Chen
Professor of Pathology Department of Pathology
University of Washington, USA
Tel: 206-616-9118
Fax: 206-543-3967
Email:
[email protected]

Received Date: October 01, 2015 Accepted Date: October 03, 2015 Published Date: October 10, 2015

Citation: Chen E (2015) Pathogenesis of Sarcomas. Diagn Pathol Open 1:e103. doi: 10.4172/2476-2024.1000e103

Copyright: © 2015 Chen E. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Visit for more related articles at Diagnostic Pathology: Open Access

Introduction

Sarcomas are rare mesenchymal malignant tumors with the incidence of about 50 per million in the general population and about 4,000 deaths every year. Clinical management is surgery with wide resection with or without adjuvant radiation and/or chemotherapy. Treatment options for relapsed or metastatic disease are still very limited. This brief editorial review will provide insights into the pathogenesis of sarcomas in terms of etiology, potential cell of origin and underlying genetic alterations.

Etiology

While the etiology of most sarcomas is unknown, some sarcomas arise in patients with cancer predisposition syndromes. For example, patients with Li Fraumeni syndrome, an autosomal dominant disorder with germline mutations in TP53, have increased susceptibility for cancers including sarcomas such osteosarcoma and rhabdomyosarcoma [1]. Patients with loss-of-heterozygosity mutations in the retinoblastoma (RB) gene are at increased risk for osteosarcoma [2]. Up to 8-13% of patients with Neurofibromatosis type 1 (NF1) will develop malignant peripheral nerve sheath tumor (MPNST) [3]. Patients with Gorlin’s syndrome (mutations in PTCH1 gene) [4,5] and Costello syndrome (mutations in HRAS gene) are susceptible for rhabdomyosarcoma [6].

Viral infection has been linked to some sarcomas. Kaposi sarcoma arises from the infection of progenitor or endothelial cell with Kaposi Sarcoma Human Herpesvirus-8 (KSHV/HHV8) [7]. Complex interactions between infected cells and dysregulated immune response likely lead to Kaposi sarcoma formation. EBV infection has been linked to the smooth muscle tumors arising in immunodeficiency with three major subtypes identified; human immunodeficiency virus (HIV)-associated, post-transplantation and association with congenital immunodeficiency syndromes [8]. The immunosuppression increases the cancer risk likely due to the lack of immune surveillance to destroy nascent tumor cells, but the underlying mechanism leading to different types of neoplasm remains to be elucidated.

Radiation-induced sarcoma is a well-known treatment-related complication and comprises about 3% of all sarcomas. The median latency is about 10 years post- radiotherapy. A wide range of radiation doses (8 to >60 Gy; median of about 50 Gy) have been reported to be associated with sarcoma formation [9]. Radiation induces genomic instability, resulting in accumulation of deleterious mutations and subsequent increased risk of malignancy. The most common type of radiation-induced sarcoma is undifferentiated pleomorphic sarcoma, not otherwise specified. Other major subtypes include angiosarcoma, leiomyosarcoma and extraskeletal osteosarcoma [9,10]. Radiationinduced sarcomas are aggressive, with prognosis thought to be worse than conventional- type sarcomas.

Cell of origin

Sarcomas likely arise from primitive, stem-cell like precursor cell population with the capacity to differentiate into multiple tissue types. This is evidenced by the subtypes with histologic features of a tissue line of differentiation but arising in locations lacking that specific tissue type, e.g. extraskeletal osteosarcoma and rhabdomyosarcoma in sites lacking skeletal muscle. Based on studies of animal models, several sarcoma types can be generated in a multipotent precursor cell lineage or a distinct cell type. For example, osteosarcoma can be generated by loss of p53 and/or Rb in a multi-potent mesenchymal lineage [11]. Embryonal rhabdomyosarcoma can be generated by adipocyte-restricted activation of sonic hedgehog signaling [12]. Overall, transdifferentiation of mesenchymal progenitor cells is a potential mechanism by which sarcomas can arise in various tissue types distinct from their histologic line of differentiation.

Genetic alterations in sarcomas

Based on genetic alterations, sarcomas can be roughly divided into two major categories; one characterized by complex karyotypes with non-specific chromosomal rearrangements, gains and losses, e.g. myxofibrosarcoma, leiomyosarcoma, and chondrosarcoma and the second characterized by simple karyotypes with specific chromosomal translocation events, e.g. synovial sarcoma, alveolar rhabdomyosarcoma and myxoid liposarcoma, or mutations, e.g. activating KIT mutations in Gastrointestinal Stromal Tumor (GIST). For sarcomas with complex genetic alterations, dysregulation of Rb, p53 and growth-factor mediated signaling pathways is frequently present [13]. A large-scale integrated sequencing, copy number and mRNA expression study of six major soft tissue sarcoma subtypes by Barretina et al. has demonstrated recurrent mutations in a subset of cases within each subtype including some targetable pathways [13]. For example, PIC3CA mutations are associated with activated AKT signaling and poor prognosis in 18% of myxoid/round cell sarcomas. Mutations in NF1 have also been detected in a subset of myxofibrosarcomas and pleomorphic liposarcomas.

As the next generation sequencing technology has been utilized more frequently in elucidating the mutational landscape of cancer genomes, the same strategy should be applied to a wider range of sarcoma subtypes to facilitate identification of potential therapeutic targets as well as molecular signatures for sarcoma pathogenesis. Recently, the Cancer Genome Atlas (TCGA) project will launch largescale genomic studies on 7 major sarcoma subtypes: dedifferentiated liposarcoma, desmoid tumor, malignant peripheral nerve sheath tumor, myxofibrosarcoma, synovial sarcoma, undifferentiated pleomorphic sarcoma. Novel biological and therapeutic insights will likely be gained from these studies.

Currently, more than 50 subtypes of sarcomas are described in the current WHO bone and soft tissue edition. With advances in molecular technologies integrating mutational and expression profiles of sarcoma genomes, additional sarcoma subtypes will likely result from molecular-based classifications. Additional molecular data will also likely translate into new prognostic parameters and therapeutic targets.

References

Select your language of interest to view the total content in your interested language
Post your comment

Share This Article

Recommended Journals

Article Usage

  • Total views: 11730
  • [From(publication date):
    March-2016 - Nov 20, 2017]
  • Breakdown by view type
  • HTML page views : 7939
  • PDF downloads : 3791

Review summary

  1. Herald Storm
    Posted on Aug 24 2016 at 3:06 pm
    The article presents the various aspects of sarcoma diagnosis as well as treatment including the etiological reasons, histopathological alterations and genetic mutations. The article also discusses the various types of sarcomas and their specific therapeutic strategies.
 

Post your comment

captcha   Reload  Can't read the image? click here to refresh

Peer Reviewed Journals
 
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
 
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

Agri & Aquaculture Journals

Dr. Krish

[email protected]

1-702-714-7001Extn: 9040

Biochemistry Journals

Datta A

[email protected]

1-702-714-7001Extn: 9037

Business & Management Journals

Ronald

[email protected]

1-702-714-7001Extn: 9042

Chemistry Journals

Gabriel Shaw

[email protected]

1-702-714-7001Extn: 9040

Clinical Journals

Datta A

[email protected]

1-702-714-7001Extn: 9037

Engineering Journals

James Franklin

[email protected]

1-702-714-7001Extn: 9042

Food & Nutrition Journals

Katie Wilson

[email protected]

1-702-714-7001Extn: 9042

General Science

Andrea Jason

[email protected]

1-702-714-7001Extn: 9043

Genetics & Molecular Biology Journals

Anna Melissa

[email protected]

1-702-714-7001Extn: 9006

Immunology & Microbiology Journals

David Gorantl

[email protected]

1-702-714-7001Extn: 9014

Materials Science Journals

Rachle Green

[email protected]

1-702-714-7001Extn: 9039

Nursing & Health Care Journals

Stephanie Skinner

[email protected]

1-702-714-7001Extn: 9039

Medical Journals

Nimmi Anna

[email protected]

1-702-714-7001Extn: 9038

Neuroscience & Psychology Journals

Nathan T

[email protected]

1-702-714-7001Extn: 9041

Pharmaceutical Sciences Journals

Ann Jose

[email protected]

1-702-714-7001Extn: 9007

Social & Political Science Journals

Steve Harry

[email protected]

1-702-714-7001Extn: 9042

 
© 2008- 2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version
adwords