{"id":16996,"date":"2022-08-30T18:12:59","date_gmt":"2022-08-30T18:12:59","guid":{"rendered":"https:\/\/admin.acceleratingscience.com\/behindthebench\/?p=16996"},"modified":"2022-08-30T18:12:59","modified_gmt":"2022-08-30T18:12:59","slug":"solving-oncology-cases-with-chromosomal-microarrays","status":"publish","type":"post","link":"https:\/\/www.thermofisher.com\/blog\/behindthebench\/solving-oncology-cases-with-chromosomal-microarrays\/","title":{"rendered":"Solving Oncology Cases With Chromosomal Microarrays"},"content":{"rendered":"

Discover the True Nature of Chromosomal Abnormalities<\/h2>\n

Oncology<\/strong> might be the discipline of medicine most deeply intertwined with complicated chromosomal abnormalities<\/strong>. In cancer, DNA repair mechanisms break down and mutations accumulate, resulting in multiple abnormalities that can be difficult to accurately identify. Each of these contributes both to the character of the cancer and the difficulty in identifying and treating its exact properties. When it comes to revealing the true nature of chromosomal abnormalities, no technique exceeds the power of chromosomal microarrays (CMAs).<\/p>\n

Dr. Madina Sukhanova, an assistant professor of pathology at Northwestern University\u2019s Feinberg School of Medicine, presents some case studies in solving difficult oncology cases using chromosomal microarrays in this webinar – Application of Chromosomal Microarray Analysis in Oncology<\/a>.<\/p>\n

\"banner<\/a><\/p>\n

The Power and Resolution of Chromosomal Microarrays (CMAs)<\/h2>\n

Working With Tumors<\/h3>\n

Dr. Sukhanova believes that the power and resolution of chromosomal microarrays<\/strong> are best deployed in the most challenging cases. They are ideal for accurately determining tumor sub classes<\/strong>, stratifying tumor risk<\/strong>, evaluating the relative danger of different tumor sites and progressions<\/strong>, and working with suboptimal samples<\/strong> such as culture failures, slowly proliferative tumor tissue, and formalin-fixed, paraffin-embedded (FFPE) samples.<\/p>\n

Drug Discovery<\/h3>\n

Microarrays can also be useful for drug discovery because of their ability to detect a large number of active sites. In these situations, they can work alongside or even replace large fluorescence in-situ<\/em> hybridization (FISH) panels, which are otherwise one of the premier oncology research tools.<\/p>\n

Detection and Characterization of Chromosomal Abnormalities<\/h3>\n

CMAs in oncology help with detecting submicroscopic deletions and duplications, detecting copy-neutral loss of heterozygosity (CN-LOH), and characterization of chromosomal abnormalities in hematologic malignancies. CMAs are also one of the best tools for studying chromothripsis<\/a>, a phenomenon in which chromosomes break into so many pieces that DNA repair mechanisms are inadequate and other detection methods produce uninterpretable results.<\/p>\n

Dr. Sukhanova makes her point with four case studies:<\/p>\n

    \n
  1. In the first, a 49-year-old woman presents with B-cell acute lymphoblastic leukemia and lymphoma related to a previous plasma cell myeloma. Her karyotype suggests that her cancer is hyperdiploid (near-complete tetraploidy related to a genome duplication event), with a good prognosis and relatively mild treatment requirements. A chromosomal microarray study revealed that what appeared to be a hyperdiploid tumor was in fact the result of a hypodiploid <\/em>tumor with substantial chromosome loss that subsequently experienced near-complete genome duplication twice, dramatically reducing the tumor\u2019s heterozygosity and giving it a chromosome count of 69-XX. While hyperdiploid lymphoma has a generally positive prognosis, hypodiploid lymphoma is a more difficult condition to treat, and her condition had more in common genetically with the latter than the former. This confirmed that the case needed much more aggressive treatment than the initial risk profile suggested.<\/li>\n
  2. In the second case, an 87-year-old woman with a previous brush with breast cancer was readmitted with plasma cell myeloma. Due to the very small number of malignant plasma cells available for study, CMA was performed alongside FISH and cytogenetic study. The chromosomal microarray revealed that the genotype of this case\u2019s cancer was quite complex, with numerous missing and duplicated chromosomes and many chromosome parts transposed onto other chromosomes or missing entirely. This was a classic case of chromothripsis, and a demonstration that CMA combined with a handful of FISH translocation probes could effectively replace a full FISH panel and detect chromothripsis.<\/li>\n
  3. The third case was a 23-month-old boy. He was born full term with no complications but presented with a persistent upper respiratory infection and unusual behavior, including an unsteady gait, recurring head pain, and fear of walking unassisted. A CT scan revealed an intracranial tumor, which was partially removed. Histology suggested a meningioma, a type of cancer virtually unheard of in children, with a median age of diagnosis of 65. Since the tumor could not be completely removed, an attempt was made to determine the tumor’s World Health Organization grade of meningioma, using cytological means. When this proved ineffective, chromosomal microarrays revealed a specific loss on chromosome 22. This information made clear that this case\u2019s prognosis was poor.<\/li>\n
  4. Sukhanova\u2019s final case was a 23-year-old woman with no significant personal medical history. She presented with a mass in her left thigh that was increasing in size. An MRI showed the mass to be heterogeneous, with some signals indicating malignancy. No residual signs of disease remained after the mass was removed, and microscopy suggested it was a rare inflammatory leiomyosarcoma\/histiocyte-rich rhabdomyoblastic tumor with a favorable prognosis. CMA was performed to get more information. In combination with other tests, this revealed that this entire category of cancer needed to be reconceptualized. The redefined “inflammatory rhabdomyoblastic tumor” has two subtypes, distinguished on the basis of whole-genome copy number assessment, with near-haploid tumors (retaining chromosomes 5, 12, 18, 20, 21, and 22) having a much worse prognosis and behavior than those exhibiting a copy-neutral loss of heterozygosity on chromosomes 5, 20, and 22. Chromosomal microarrays have proven to be the best way to distinguish these two disease subtypes. The case proved to have the former type. The CMA and immunohistochemistry together confirmed that this case\u2019s seemingly low-risk situation was actually much higher-risk and merited longer-term chemotherapy to prevent dangerous recurrence.<\/li>\n<\/ol>\n

    Related<\/strong>: Chromothripsis: A New Frontier in Cancer Research<\/a><\/p>\n

    CMA Generates Data About Precise Chromosomal Variations<\/h2>\n

    CMA is a powerful tool that generates data about precise chromosomal variations that are often difficult to detect by other methods, and that makes it ideal for the task of differentiating between cancer subtypes whose distinctions are often subtle but very meaningful. It is evident that chromosomal microarrays are an important piece of the toolkit for accurate tumor subclassification, instrumental in assessment of risk, helpful in comparative analysis of genetic signatures of different tumor sites, and excellent for oncology clinical research.<\/p>\n

    \u00bb Watch:<\/strong> Application of Chromosomal Microarray Analysis in Oncology<\/a><\/h3>\n

    Dr. Madina Sukhanova demonstrates the utility of CMA combined with NGS assays to identify genetic aberrations associated with specific prognoses in different types of cancer.<\/p>\n

      \n
    • Learn how to investigate interesting oncology cases and findings<\/li>\n
    • Gain working knowledge of the importance of CMA and how it plays a vital role in oncology testing<\/li>\n
    • Discover the utility of CMA combined with NGS<\/li>\n<\/ul>\n","protected":false},"excerpt":{"rendered":"

      Discover the True Nature of Chromosomal Abnormalities Oncology might be the discipline of medicine most deeply intertwined with complicated chromosomal abnormalities. In cancer, DNA repair mechanisms break down and mutations accumulate, resulting in multiple abnormalities that can be difficult to accurately identify. Each of these contributes both to the character of the cancer and the<\/p>\n","protected":false},"author":120,"featured_media":17009,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"_kad_blocks_custom_css":"","_kad_blocks_head_custom_js":"","_kad_blocks_body_custom_js":"","_kad_blocks_footer_custom_js":"","_monsterinsights_skip_tracking":false,"_genesis_hide_title":false,"_genesis_hide_breadcrumbs":false,"_genesis_hide_singular_image":false,"_genesis_hide_footer_widgets":false,"_genesis_custom_body_class":"","_genesis_custom_post_class":"","_genesis_layout":"","_jetpack_newsletter_access":"","_jetpack_dont_email_post_to_subs":false,"_jetpack_newsletter_tier_id":0,"_jetpack_memberships_contains_paywalled_content":false,"_jetpack_memberships_contains_paid_content":false,"footnotes":""},"categories":[54],"tags":[271,1844,2277,2300,112],"division":[],"class_list":{"0":"post-16996","1":"post","2":"type-post","3":"status-publish","4":"format-standard","5":"has-post-thumbnail","7":"category-cancer-research","8":"tag-cancer","9":"tag-cancer-research","10":"tag-microarray","11":"tag-oncology","12":"tag-oncology-research","13":"entry"},"_selected_authors":"","_selected_reviewers":"","acf":[],"yoast_head":"\nSolving Oncology Cases With Chromosomal Microarrays<\/title>\n<meta name=\"description\" content=\"The power and resolution of chromosomal microarrays (CMAs) are deployed in the most challenging cases. 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