Molecular diagnosis of soft tissue neoplasia: clinical applications and recent advances

Abstract

Sarcomas are rare and heterogeneous neoplasms of mesenchymal tissues with diverse morphologies and clinical behavior. In the last few years, the discovery of specific genetic aberrations in these tumors has allowed better classification and understanding of mechanisms driving their pathogenesis. While the majority of sarcomas are still treated by traditional modalities, molecular markers driving the pathogenesis have paved the way for more accurate diagnosis and opportunity to explore other therapeutic strategies. This review discusses the available molecular tools in sarcoma diagnostics and highlight some of the biological significance of the recent discoveries and their clinical applications.

Keywords::

• FISH
• fusion genes
• gene network
• next-generation sequencing
• RT-PCR
• soft tissue sarcoma
• therapeutics

Acknowledgements

The author thanks K Nafa for assistance with RT-PCR images and S Cook for editorial assistance.

Financial & competing interests disclosure

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Soft tissue tumors are rare diverse and heterogeneous neoplasms, which frequently pose diagnostic difficulties for the pathologist.

• Current classification is based on histological subtypes related to tissue of origin and morphological appearance of cell types.

• Immunohistochemical antibodies are commonly used to identify specific categories; however, can be challenging due to overlapping expression and lack of lineage specificity in most instances.

• Cytogenetic methods and routine karyotyping have unveiled many disease-associated translocations over many decades.

• Genetic alterations classify sarcomas into three major types: sarcomas with simple karyotypes (translocation-associated), sarcomas with complex karyotypes and sarcomas with point mutations and/or amplifications.

• About 20% of soft tissue tumors show characteristic genetic aberrations.

• Fusion genes are used as diagnostic markers in many sarcoma subtypes.

• However, promiscuity of the genes with the ability to form multiple fusion partners (e.g., EWSR1) remains a diagnostic caveat.

• The same fusion gene transcript can be seen in two or three different tumor types underscoring the importance of interpretation in context of the disease process.

• Novel fusion genes are being discovered at a rapid pace with the advent of new and sophisticated technologies such as next-generation sequencing.

• Teamwork is essential to interpret the vast amount of data produced by these new technologies so that meaningful information can be deciphered for diagnosis, prognosis and therapeutics.

Notes