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Int J Clin Exp Pathol 2010;3(4):416-429
Review Article
Molecular classification of soft tissue sarcomas and its clinical applications
Shilpa Jain, Ruliang Xu, Victor G. Prieto, Peng Lee
Department of Pathology and Dermatology, New York University School of Medicine, New York Harbor Healthcare System, New York, New York
and Department of Pathology, UT, M. D. Anderson Cancer Center, Houston TX, USA
Received March 21, 2010, accepted April 15, 2010, available online April 23, 2010
Abstract: Sarcomas are a heterogeneous group of tumors that are traditionally classified according to the morphology and type of tissue that
they resemble, such as rhabdomyosarcoma, which resembles skeletal muscle. However, the cell of origin is unclear in numerous sarcomas.
Molecular genetics analyses have not only assisted in understanding the molecular mechanism in sarcoma pathogenesis but also
demonstrated new relationships within different types of sarcomas leading in many cases to a more proper classification of sarcomas.
Molecular classification based on the genetic alteration divides sarcoma into two main categories: (i) sarcomas with specific genetic
alterations; which can further be subclassified based on a) reciprocal translocations resulting in oncogenic fusion transcripts (e.g.
EWSR1-FLI1 in Ewing sarcoma) and b) specific oncogenic mutations (e.g. KIT and PDGFRA mutations in gastrointestinal stromal tumors) and
(ii) sarcomas displaying multiple, complex karyotypic abnormalities with no specific pattern, including leiomyosarcoma, and pleomorphic
liposarcoma. These specific genetic alterations are an important adjunct to standard morphological and immunohistochemical diagnoses,
and in some cases have a prognostic value, e. g., Ewing family tumors, synovial sarcoma, and alveolar rhabdomyosarcoma. In addition, these
studies may also serve as markers to detect minimal residual disease and can aid in staging or monitor the efficacy of therapy. Furthermore,
sarcoma-specific fusion genes and other emerging molecular events may also represent potential targets for novel therapeutic approaches
such as Gleevec for dermatofibrosarcoma protuberans. Therefore, increased understanding of the molecular biology of sarcomas is leading
towards development of newer and more effective treatment regimens. The review focuses on recent advances in molecular genetic alterations
having an impact on diagnostics, prognostication and clinical management of selected sarcomas. (IJCEP1003008).
Keywords: Sarcomas, specific genetic translocation, molecular genetics
Full text PDF
Address all correspondence to:
Victor Prieto, MD, PhD
Department of Pathology
UT, MD Anderson Cancer Center
1515 Holcombe Blvd
Houston, TX 77030
Phone: (713) 792-3187
E-mail: vprieto@mdanderson.org
or
Peng Lee, MD, PhD
Department of Pathology and Urology
New York University School of Medicine,
560 First Avenue,
New York, NY 10010
Phone: (212)-9513418
E-mail: peng.lee@nyumc.org
Review Article
Molecular classification of soft tissue sarcomas and its clinical applications
Shilpa Jain, Ruliang Xu, Victor G. Prieto, Peng Lee
Department of Pathology and Dermatology, New York University School of Medicine, New York Harbor Healthcare System, New York, New York
and Department of Pathology, UT, M. D. Anderson Cancer Center, Houston TX, USA
Received March 21, 2010, accepted April 15, 2010, available online April 23, 2010
Abstract: Sarcomas are a heterogeneous group of tumors that are traditionally classified according to the morphology and type of tissue that
they resemble, such as rhabdomyosarcoma, which resembles skeletal muscle. However, the cell of origin is unclear in numerous sarcomas.
Molecular genetics analyses have not only assisted in understanding the molecular mechanism in sarcoma pathogenesis but also
demonstrated new relationships within different types of sarcomas leading in many cases to a more proper classification of sarcomas.
Molecular classification based on the genetic alteration divides sarcoma into two main categories: (i) sarcomas with specific genetic
alterations; which can further be subclassified based on a) reciprocal translocations resulting in oncogenic fusion transcripts (e.g.
EWSR1-FLI1 in Ewing sarcoma) and b) specific oncogenic mutations (e.g. KIT and PDGFRA mutations in gastrointestinal stromal tumors) and
(ii) sarcomas displaying multiple, complex karyotypic abnormalities with no specific pattern, including leiomyosarcoma, and pleomorphic
liposarcoma. These specific genetic alterations are an important adjunct to standard morphological and immunohistochemical diagnoses,
and in some cases have a prognostic value, e. g., Ewing family tumors, synovial sarcoma, and alveolar rhabdomyosarcoma. In addition, these
studies may also serve as markers to detect minimal residual disease and can aid in staging or monitor the efficacy of therapy. Furthermore,
sarcoma-specific fusion genes and other emerging molecular events may also represent potential targets for novel therapeutic approaches
such as Gleevec for dermatofibrosarcoma protuberans. Therefore, increased understanding of the molecular biology of sarcomas is leading
towards development of newer and more effective treatment regimens. The review focuses on recent advances in molecular genetic alterations
having an impact on diagnostics, prognostication and clinical management of selected sarcomas. (IJCEP1003008).
Keywords: Sarcomas, specific genetic translocation, molecular genetics
Full text PDF
Address all correspondence to:
Victor Prieto, MD, PhD
Department of Pathology
UT, MD Anderson Cancer Center
1515 Holcombe Blvd
Houston, TX 77030
Phone: (713) 792-3187
E-mail: vprieto@mdanderson.org
or
Peng Lee, MD, PhD
Department of Pathology and Urology
New York University School of Medicine,
560 First Avenue,
New York, NY 10010
Phone: (212)-9513418
E-mail: peng.lee@nyumc.org
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