Abstract
The bone and bone marrow are common sites for metastasis due to their high vascularity and niche components. The commonest primaries in adults are the lung, prostate, and breast. Neuroblastoma, osteosarcoma, and Ewing sarcoma are the most frequent in children. The mechanism of tumor spread involves a multistep process with underlying molecular changes involving the interaction between tumor cells and the marrow microenvironment. Sometimes metastatic spread to the bone marrow manifests in peripheral blood changes, including cytopenia and leucoerythroblastic changes, in which case the bone marrow may be the first tissue diagnosis of the tumor. The bone marrow morphology and IHC help identify the primary tumor, though it remains unknown in some cases. The presence of metastasis often implies a poor prognosis.
Key Terms in this Chapter
Epithelial-to-Mesenchymal Transition (EMT): A biological process where epithelial cells, which are typically characterized by their tight connections and organized structure, transform into mesenchymal stem cells. These mesenchymal cells can migrate and invade, as they lose their cell polarity and cell-cell adhesion properties. They play a significant role in cancer progression, particularly the initiation of metastasis.
Clonal Tracking: In the context of cancer and metastasis refers to studying the evolutionary dynamics of tumor clones using techniques such as viral-based and CRISPR-Cas9-based cellular barcoding, lineage tracing, and imaging-based approaches It allows tracing the growth patterns, genetic changes, and heterogeneity of cancer cells within a tumor, giving insights into disease progression, treatment resistance, and potential therapeutic targets.
Genome-Wide Cell-Free Fragmentome Features: Fragmentation profiles allow the detection of specific genomic and chromatin characteristics in specific tumors, e.g., hepatocellular carcinoma allowing the screening of individuals at high risks, such as those with cirrhosis and viral hepatitis.
Tumor-Secreted Exosomes: Small extracellular vesicles, that are released by tumor cells into the surrounding environment, carrying a variety of molecules, including proteins, DNA, RNA, and lipids. They promote tumor growth, metastasis, and therapy resistance by transferring oncogenic substances between cancer cells and other cells within the tumor microenvironment .
CRISPR-Associated Protein (Cas): S group of proteins crucial to recognizing and binding to specific DNA sequences, guided by CRISPR RNA (crRNA). The best-known Cas protein is Cas9, which, when combined with crRNA, forms the basis of the widely used CRISPR-Cas9 genome editing technology. Cas proteins are essential for cutting DNA at specific sites, allowing researchers to edit genes precisely.
Phylogenetic ctDNA Analysis: A powerful approach used to profile circulating tumor DNA (ctDNA) in early-stage lung cancer. It allows tracking the evolutionary dynamics of cancer non-invasively by examining the genetic changes within ctDNA.
Exosomes: These can be found in various biological fluids and their composition reflects the cellular origin. Thus, tumor-secreted exosomes have distinct molecular signatures that can be used for diagnostic purposes or as therapeutic targets.
Extracellular Vesicle–Based Protein Assay: Extracellular vesicles are circulating biomarkers containing other biomolecules, such as DNA, RNA, metabolites, and lipids, enclosed by lipid bilayer membranes and detected with microarray staining. Release of extracellular vesicles occurs in early tumorigenesis by tumor cells and thus allows early tumor screening.