Soft Tissue Sarcoma: An Insight on Biomarkers at Molecular, Metabolic and Cellular Level

Abstract

Soft tissue sarcomas (STSs) are a heterogeneous group of rare tumors. Although constituting only 1% of all human malignancies, STSs represent the second most common type of solid tumors in children and adolescents and comprise an important group of secondary malignancies. Over 100 histologic subtypes have been characterized to date (occurring predominantly in the trunk, extremity, and retroperitoneum), and many more are being discovered due to molecular profiling. STS mortality remains high, despite adjuvant chemotherapy. New prognostic stratification markers are needed to help identify patients at risk of recurrence and possibly apply more intensive or novel treatments. Recent scientific advancements have enabled a more precise molecular characterization of sarcoma subtypes and revealed novel therapeutic targets and prognostic/predictive biomarkers. This review aims at providing a comprehensive overview of the most relevant cellular, molecular and metabolic biomarkers for STS, and highlight advances in STS-related biomarker research.

Inflammatory leiomyosarcoma/rhabdomyoblastic tumor: A report of two cases with novel genetic findings

“…This variant c.3172+1G>T in MSH6 disrupts a donor splice site in intron 4 is expected to affect mRNA processing and lead to aberrant splicing with resulting exon‐skipping events and protein truncation. This particular change was reported in individuals affected with Lynch syndrome and is reported in five entries in ClinVar (Variation ID: 89344) as a variant of clinical significance 15 . Follow‐up immunohistochemical testing showed loss of the MSH6 protein in tumor and non‐tumor tissue, confirming the functional deficiency in this patient's tumor.…”

“…Mutations of the NF1 tumor suppressor gene predispose individuals to a variety of benign and malignant tumors, including rhabdomyosarcoma. 15 Our study is the first one to demonstrate TP53 mutations in ILMS/ An additional mutation detected in our study was a frameshift variant in SMARCA4 (19p13.2), which encodes an ATPase subunit of BAF chromatin-remodeling complexes. Inactivation of SMARCA4 has been reported in a wide variety of cancers and is often characterized by a high-grade undifferentiated or rhabdoid histomorphology as seen in small cell carcinoma of the ovary hypercalcemic type and SMARCA4-deficient thoracic and uterine sarcomas.…”

“…TP53 plays a critical role in protecting the cell from the transformative effects of DNA damage by inducing cell-cycle arrest and apoptosis. Loss of TP53 function is associated with genomic instability and the development of aneuploidy in cancer [15][16][17][18][19][20][21]. An interesting association is loss of TP53 together with hypodiploidy.…”

Retroperitoneal Sarcoma Care in 2021

“…The progress in our understanding of the immune components of STS has led to the development of immune checkpoint inhibitors, activated NK cells, and CART T cells, also illustrated in this review. The authors have taken one step further to outline the cellular, molecular and metabolic biomarkers [ 113 , 114 ]. To further personalize care based on molecular profiling, many randomized control trials are underway.…”

Chip-Based and Wearable Tools for Isothermal Amplification and Electrochemical Analysis of Nucleic Acids

“…Indeed, the recent coronavirus pandemic has demonstrated how nucleic acid detection methods have become a gold-standard technology for virus and microbial detection. Furthermore, liquid biopsy and the subsequent determination of circulating nucleic acids have emerged as a challenging approach for the early detection of cancer and its recurrence, or for monitoring the response to therapy and drug resistance [1][2][3]. This attractive concept has been integrated in cancer management due to the recent implementation of extremely sensitive and selective analytical genomic methodologies and bioinformatics tools.…”