Challenges in Stratifying the Molecular Variability of Patient-Derived Colon Tumor Xenografts

Joint Authors

Małgorzata, Statkiewicz
Michal, Mikula
Jerzy, Ostrowski
Cybulska, Magdalena
Olesinski, Tomasz
Goryca, Krzysztof
Paczkowska, Katarzyna
Kopczynski, Michal
Grochowska, Aleksandra
Unrug-Bielawska, Katarzyna
Tyl-Bielicka, Anita
Gajewska, Marta
Mroz, Andrzej
Dabrowska, Michalina
Karczmarski, Jakub
Paziewska, Agnieszka
Zając, Leszek
Bednarczyk, Mariusz

Source

BioMed Research International

Issue

Vol. 2018, Issue 2018 (31 Dec. 2018), pp.1-9, 9 p.

Publisher

Hindawi Publishing Corporation

Publication Date

2018-12-19

Country of Publication

Egypt

No. of Pages

9

Main Subjects

Medicine

Abstract EN

Colorectal cancer (CRC) is the second most common cancer in Europe and a leading cause of death worldwide.

Patient-derived xenograft (PDX) models maintain complex intratumoral biology and heterogeneity and therefore remain the platform of choice for translational drug discovery.

In this study, we implanted 37 primary CRC tumors and five CRC cell lines into NU/J mice to develop xenograft models.

Primary tumors and established xenografts were histologically assessed and surveyed for genetic variants and gene expression using a panel of 409 cancer-related genes and RNA-seq, respectively.

More than half of CRC tumors (20 out of 37, 54%) developed into a PDX.

Histological assessment confirmed that PDX grading, stromal components, inflammation, and budding were consistent with those of the primary tumors.

DNA sequencing identified an average of 0.14 variants per gene per sample.

The percentage of mutated variants in PDXs increased with successive passages, indicating a decrease in clonal heterogeneity.

Gene Ontology analyses of 4180 differentially expressed transcripts (adj.

p value < 0.05) revealed overrepresentation of genes involved in cell division and catabolic processes among the transcripts upregulated in PDXs; downregulated transcripts were associated with GO terms related to extracellular matrix organization, immune responses, and angiogenesis.

Neither a transcriptome-based consensus molecular subtype (CMS) classifier nor three other predictors reliably matched PDX molecular subtypes with those of the primary tumors.

In sum, both genetic and transcriptomic profiles differed between donor tumors and PDXs, likely as a consequence of subclonal evolution at the early phase of xenograft development, making molecular stratification of PDXs challenging.

American Psychological Association (APA)

Cybulska, Magdalena& Olesinski, Tomasz& Goryca, Krzysztof& Paczkowska, Katarzyna& Małgorzata, Statkiewicz& Kopczynski, Michal…[et al.]. 2018. Challenges in Stratifying the Molecular Variability of Patient-Derived Colon Tumor Xenografts. BioMed Research International،Vol. 2018, no. 2018, pp.1-9.
https://search.emarefa.net/detail/BIM-1125539

Modern Language Association (MLA)

Cybulska, Magdalena…[et al.]. Challenges in Stratifying the Molecular Variability of Patient-Derived Colon Tumor Xenografts. BioMed Research International No. 2018 (2018), pp.1-9.
https://search.emarefa.net/detail/BIM-1125539

American Medical Association (AMA)

Cybulska, Magdalena& Olesinski, Tomasz& Goryca, Krzysztof& Paczkowska, Katarzyna& Małgorzata, Statkiewicz& Kopczynski, Michal…[et al.]. Challenges in Stratifying the Molecular Variability of Patient-Derived Colon Tumor Xenografts. BioMed Research International. 2018. Vol. 2018, no. 2018, pp.1-9.
https://search.emarefa.net/detail/BIM-1125539

Data Type

Journal Articles

Language

English

Notes

Includes bibliographical references

Record ID

BIM-1125539