Abstract 162: Genomic analysis of uterine aspirates improves diagnosis and captures the intratumor heterogeneity in endometrial cancer

Background: Among the claudin (CLDN) family, CLDN6 exhibits aberrant expression in various cancers, but its biological relevance has not yet been established. We generated a monoclonal antibody (mAb) against human CLDN6 and verified its specificity. By immunohistochemical staining and semi-quantification, we evaluated the relationship between CLDN6 expression and clinicopathological parameters in tissues from 173 cases of endometrial cancer. Results: The established mAb selectively recognized CLDN6 protein. Ten of the 173 cases (5.8%) showed high CLDN6 expression (score 3+), whereas 19 (11.0%), 18 (10.4%) and 126 (72.4%) cases revealed low CLDN6 expression (score 2+, 1+ and 0, respectively). In addition, intratumor heterogeneity of CLDN6 expression was observed even in the cases with high CLDN6 expression. The 5-year survival rates in the high and low CLDN6 groups was approximately 30% and 90%, respectively. Among the clinicopathological factors, the high CLDN6 expression was significantly associated with surgical stage III/IV, histological type, histological grade 3, lymphovascular space involvement, lymph node metastasis and distant metastasis. Furthermore, the high CLDN6 expression was an independent prognostic marker for overall survival of endometrial cancer patients (hazard ratio 3.50, p = 0.014). Conclusions: It can be concluded that aberrant CLDN6 expression is useful to predict poor outcome for endometrial cancer and might be a promising therapeutic target.

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Serial genomic analysis of endometrium supports the existence of histologically indistinct endometrial cancer precursors

The Journal of Pathology ◽

10.1002/path.5628 ◽

2021 ◽

Author(s):

Mitzi Aguilar ◽

He Zhang ◽

Musi Zhang ◽

Brandi Cantarell ◽

Subhransu S. Sahoo ◽

...

Keyword(s):

Endometrial Cancer ◽

Genomic Analysis ◽

Cancer Precursors

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Modeling colorectal cancer evolution

Journal of Human Genetics ◽

10.1038/s10038-021-00930-0 ◽

2021 ◽

Author(s):

Atsushi Niida ◽

Koshi Mimori ◽

Tatsuhiro Shibata ◽

Satoru Miyano

Keyword(s):

Mathematical Modeling ◽

Colorectal Cancer ◽

Early Stage ◽

Technological Development ◽

Acquired Resistance ◽

Genomic Analysis ◽

Evolutionary Model ◽

Intratumor Heterogeneity ◽

Cancer Evolution ◽

Neutral Mutations

AbstractUnderstanding cancer evolution provides a clue to tackle therapeutic difficulties in colorectal cancer. In this review, together with related works, we will introduce a series of our studies, in which we constructed an evolutionary model of colorectal cancer by combining genomic analysis and mathematical modeling. In our model, multiple subclones were generated by driver mutation acquisition and subsequent clonal expansion in early-stage tumors. Among the subclones, the one obtaining driver copy number alterations is endowed with malignant potentials to constitute a late-stage tumor in which extensive intratumor heterogeneity is generated by the accumulation of neutral mutations. We will also discuss how to translate our understanding of cancer evolution to a solution to the problem related to therapeutic resistance: mathematical modeling suggests that relapse caused by acquired resistance could be suppressed by utilizing clonal competition between sensitive and resistant clones. Considering the current rate of technological development, modeling cancer evolution by combining genomic analysis and mathematical modeling will be an increasingly important approach for understanding and overcoming cancer.

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Abstract PR007: Genomic characterization of endometrial cancer patient-derived xenografts reveals intratumor heterogeneity

10.1158/1557-3265.endomet20-pr007 ◽

2021 ◽

Author(s):

Olga Kondrashova ◽

Vanessa F. Bonazzi ◽

Deborah Smith ◽

Katia Nones ◽

Asmerom Sengal ◽

...

Keyword(s):

Endometrial Cancer ◽

Cancer Patient ◽

Intratumor Heterogeneity ◽

Endometrial Cancer Patient ◽

Genomic Characterization

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Genomic analysis of C-type lectins

Biochemical Society Symposium ◽

10.1042/bss0690059 ◽

2002 ◽

Vol 69 ◽

pp. 59-72 ◽

Cited By ~ 85

Author(s):

Kurt Drickamer ◽

Andrew J. Fadden

Keyword(s):

Biological Effects ◽

Cell Signalling ◽

Genomic Analysis ◽

Binding Activity ◽

Immunoglobulin Superfamily ◽

Carbohydrate Binding ◽

Carbohydrate Recognition ◽

Calcium Dependent ◽

Binding Domains ◽

Carbohydrate Recognition Domains

Many biological effects of complex carbohydrates are mediated by lectins that contain discrete carbohydrate-recognition domains. At least seven structurally distinct families of carbohydrate-recognition domains are found in lectins that are involved in intracellular trafficking, cell adhesion, cell–cell signalling, glycoprotein turnover and innate immunity. Genome-wide analysis of potential carbohydrate-binding domains is now possible. Two classes of intracellular lectins involved in glycoprotein trafficking are present in yeast, model invertebrates and vertebrates, and two other classes are present in vertebrates only. At the cell surface, calcium-dependent (C-type) lectins and galectins are found in model invertebrates and vertebrates, but not in yeast; immunoglobulin superfamily (I-type) lectins are only found in vertebrates. The evolutionary appearance of different classes of sugar-binding protein modules parallels a development towards more complex oligosaccharides that provide increased opportunities for specific recognition phenomena. An overall picture of the lectins present in humans can now be proposed. Based on our knowledge of the structures of several of the C-type carbohydrate-recognition domains, it is possible to suggest ligand-binding activity that may be associated with novel C-type lectin-like domains identified in a systematic screen of the human genome. Further analysis of the sequences of proteins containing these domains can be used as a basis for proposing potential biological functions.

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