Pericentric inversion of the human Y chromosome has been reported infrequently but it is known to be an inherited anomaly. Several Harris, 1970) that both sexes were affected; the parents were first cousins, and the affected boys and their normal father had a pericentric inversion of the Y chromosome. The present study was done in an attempt to find the origin of the unusual Y chromosome. Family StudyThe family, whose pedigree is shown in Fig. 1 (Fig. 4). There was little difference in the number of interphase nuclei showing a Y-spot; the highest score was 22% positive and the mean score of all buccal and lymphocyte preparations was 7%.

e18579 Background: Patients with anaplastic thyroid cancer (ATC) have poor outcomes due to treatment resistance with an estimated 5-year survival rate of 7%. Although “classic” ATC can arise de novo from follicular thyroid cells, it can also arise in association with papillary thyroid carcinoma (PTC), as a “mixed” histology. The immunologic and molecular differences between these histological subtypes have not been well-characterized. We aimed to investigate the differences in immune signatures in these histological subtypes to assess immune pathway differences in the classic ATC and mixed ATC/PTC tumor microenvironment. Methods: Classic ATC and mixed ATC/PTC cases (N = 12) from 1998 to 2018 with viable formalin-fixed paraffin-embedded (FFPE) tissue were identified and selected by a board-certified pathologist. 4 samples exhibited both PTC and ATC components while 8 were classic ATC cases, as confirmed by a pathologist. In the 4 mixed ATC/PTC histology specimens, 3 were identified to contain greater than 80% ATC involvement while the fourth was characterized as 40% ATC and 60% PTC. The NanoString Immune Profiling panel contains more than 770 genes. It was performed with extracted RNA to evaluate and compare the gene expression of classic ATC versus mixed ATC/PTC. Results: Majority of patients (N = 11) developed metastatic disease, a common feature of ATC, and are currently deceased (N = 10). The NanoString panel identified several differentially expressed immune pathways in the mixed ATC/PTC in comparison to the classic ATC group. There is upregulation of CD3 (p < 0.01) and CD8 (p < 0.01) transcripts in the mixed ATC/PTC group, but not CD4 transcripts (p > 0.05). Additionally, we found that genes associated with B cell and T cell function were significantly upregulated in the mixed ATC group, including CD27 (p < 0.01), CD28 (p < 0.05), BTLA (p < 0.01), CTLA4 (p < 0.01), LAG3 (p < 0.05), and TIGIT(p < 0.01). We did not observe any significant differences in the expression of PD1 (p > 0.05) or MR1 (p > 0.05) between classic ATC and mixed ATC variants. Conclusions: Our study demonstrates a significant difference in the immune landscape between classic and mixed variants of ATC. Our results indicate there may be an increase in immune cell infiltration and tumor inflammation in the mixed ATC variant, which suggests patients with the mixed ATC variant may show a positive response to immunotherapy.

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Introduction: Epithelial-mesenchymal transition (EMT) plays a major role in invasion, migration, and drug resistance in cancer. There are several signaling pathways associated with EMT, including PI3K/Akt and NFΚB. EMT is present in several cancer types, especially in the recurrent and metastatic setting. Anaplastic thyroid cancer (ATC) accounts for 2% of thyroid cancers and are notoriously aggressive. Clinically, these patients have poor survival rates and are resistant to standard of care therapies. ATC can arise de novo from follicular thyroid cells or in association with papillary thyroid carcinoma (PTC). Therefore, we investigated the differences in gene signature and cancer pathway expression in these histological subtypes, and their potential association with genes upregulated in EMT. Methods: De novo ATC and mixed ATC/PTC cases (N=12) from 1998 to 2018 with viable formalin-fixed paraffin-embedded (FFPE) tissue were identified and selected. 8 cases exhibited both PTC and ATC components while the rest (N=4) were pure ATC cases, as confirmed by a pathologist. In the 4 mixed ATC/PTC histology group specimen, 3 were identified by a pathologist to contain greater than 80% ATC involvement while the fourth was characterized as 40% ATC and 60% PTC. The NanoString PanCancer Pathway panel, which contains 770 genes from 13 signaling pathways, was performed with the extracted tumor RNA to evaluate and compare the gene signatures of the pure ATC versus mixed ATC/PTC cases. Results: Majority of patients (N=11, 92%) developed metastatic disease, a common feature of ATC, and are currently deceased (N=10, 83%). Using Nanostring panel on the patient specimen, we identified differential expression of genes and cancer pathways in the mixed ATC/PTC cohort in comparison to the pure ATC cohort. 28 genes, strongly associated with cancer pathways including MAPK, cell cycle-apoptosis, driver genes, and RAS, were significantly upregulated with at least two-fold change in the mixed ATC/PTC histology group in comparison to the pure ATC histology group (p&lt;0.01). Three genes strongly linked with EMT demonstrated increased expression. MMP3 was the most upregulated gene in the mixed ATC/PTC histology group, with a 41.4 linear fold change (p=0.001), and has been shown to induce EMT in various cancers. Two other EMT-related genes, TNF and PIK3CG, were similarly significantly expressed in the mixed ATC/PTC versus the pure ATC histology group (p&lt;0.005). Conclusion: Our results demonstrate a significant difference in the expression of cancer-related genes between the mixed ATC/PTC and the pure ATC histology groups. Our findings also suggest a correlation between mixed ATC/PTC histology cases and genes associated with EMT. Citation Format: Rebecca R. Pharaon, Hannah J. Young, Kimberley-Jane C. Bonjoc, Feras Ally, Holly Yin, Robert Kang, Thomas Gernon, Ammar Chaudhry, Ellie Maghami. Upregulation of genes linked to epithelial-mesenchymal transition in anaplastic thyroid cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1525.

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