9. Solid Tumors [Breast and HER2 amp; Lung (ALK/ROS/RET)] Ondemand-C09 Solid Tumors Dubuc

C09 Solid Tumors Dubuc

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This document discusses the cytogenetics of solid tumors, with a focus on the mechanisms of tumorigenesis, current assays and limitations, and actionable alterations. Cancer is described as a multi-step process involving acquired aberrations that lead to uncontrolled cell growth. Tumor suppressor genes and oncogenes are explained as genes that control and promote cell growth, respectively. The role of chromosomal abnormalities in tumor development is attributed to the work of Theodor Boveri, who postulated that improper chromosome segregation could lead to changes in growth.<br /><br />Cytogenetic analysis of solid tumors has been successful in identifying recurrent chromosomal changes, such as those seen in myxoid liposarcomas and synovial sarcoma. These findings have led to further molecular characterization and identification of driver genes. Challenges in cytogenetic analysis include factors like microbial contamination, tumor necrosis, and variable growth patterns. However, the development of fluorescence in situ hybridization (FISH) has allowed for evaluation of fixed materials and non-dividing cells, overcoming some of these challenges.<br /><br />Different testing options are available today, including FISH, karyotyping, microarray, and sequencing. Each option has its strengths and weaknesses, with FISH being useful for rapid diagnostic evaluations of specific findings, while microarray provides genome-wide copy number analysis. Specific examples discussed include the discovery of ALK rearrangements in anaplastic large cell lymphoma and the use of Crizotinib to target these rearrangements. The document also mentions the algorithmic testing used for HER2 amplification in breast cancer.<br /><br />In conclusion, cytogenetic studies have played a significant role in the identification of pathognomonic structural rearrangements in solid tumors, leading to a better understanding of the underlying mechanisms and potential therapeutic targets. These studies have been facilitated by advancements in techniques such as FISH and microarray analysis.

Keywords

cytogenetics

solid tumors

tumorigenesis

chromosomal abnormalities

FISH

microarray

driver genes

ALK rearrangements

HER2 amplification

therapeutic targets