Elucidating the transcriptional program of feline injection-site sarcoma using a cross-species mRNA-sequencing approach
Abstract Background Feline injection-site sarcoma (FISS), an aggressive iatrogenic subcutaneous malignancy, is challenging to manage clinically and little is known about the molecular basis of its pathogenesis. Tumor transcriptome profiling has proved valuable for gaining insights into the molecular...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2019-04-01
|
| Series: | BMC Cancer |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12885-019-5501-z |
| _version_ | 1819158660023058432 |
|---|---|
| author | Qi Wei Stephen A. Ramsey Maureen K. Larson Noah E. Berlow Donasian Ochola Christopher Shiprack Amita Kashyap Bernard Séguin Charles Keller Christiane V. Löhr |
| author_facet | Qi Wei Stephen A. Ramsey Maureen K. Larson Noah E. Berlow Donasian Ochola Christopher Shiprack Amita Kashyap Bernard Séguin Charles Keller Christiane V. Löhr |
| author_sort | Qi Wei |
| collection | DOAJ |
| description | Abstract Background Feline injection-site sarcoma (FISS), an aggressive iatrogenic subcutaneous malignancy, is challenging to manage clinically and little is known about the molecular basis of its pathogenesis. Tumor transcriptome profiling has proved valuable for gaining insights into the molecular basis of cancers and for identifying new therapeutic targets. Here, we report the first study of the FISS transcriptome and the first cross-species comparison of the FISS transcriptome with those of anatomically similar soft-tissue sarcomas in dogs and humans. Methods Using high-throughput short-read paired-end sequencing, we comparatively profiled FISS tumors vs. normal tissue samples as well as cultured FISS-derived cell lines vs. skin-derived fibroblasts. We analyzed the mRNA-seq data to compare cancer/normal gene expression level, identify biological processes and molecular pathways that are associated with the pathogenesis of FISS, and identify multimegabase genomic regions of potential somatic copy number alteration (SCNA) in FISS. We additionally conducted cross-species analyses to compare the transcriptome of FISS to those of soft-tissue sarcomas in dogs and humans, at the level of cancer/normal gene expression ratios. Results We found: (1) substantial differential expression biases in feline orthologs of human oncogenes and tumor suppressor genes suggesting conserved functions in FISS; (2) a genomic region with recurrent SCNA in human sarcomas that is syntenic to a feline genomic region of probable SCNA in FISS; and (3) significant overlap of the pattern of transcriptional alterations in FISS with the patterns of transcriptional alterations in soft-tissue sarcomas in humans and in dogs. We demonstrated that a protein, BarH-like homeobox 1 (BARX1), has increased expression in FISS cells at the protein level. We identified 11 drugs and four target proteins as potential new therapies for FISS, and validated that one of them (GSK-1059615) inhibits growth of FISS-derived cells in vitro. Conclusions (1) Window-based analysis of mRNA-seq data can uncover SCNAs. (2) The transcriptome of FISS-derived cells is highly consistent with that of FISS tumors. (3) FISS is highly similar to soft-tissue sarcomas in dogs and humans, at the level of gene expression. This work underscores the potential utility of comparative oncology in improving understanding and treatment of FISS. |
| first_indexed | 2024-12-22T16:28:11Z |
| format | Article |
| id | doaj.art-4e3748806409438a85f88ef51630cd0b |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-12-22T16:28:11Z |
| publishDate | 2019-04-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-4e3748806409438a85f88ef51630cd0b2022-12-21T18:20:07ZengBMCBMC Cancer1471-24072019-04-0119111810.1186/s12885-019-5501-zElucidating the transcriptional program of feline injection-site sarcoma using a cross-species mRNA-sequencing approachQi Wei0Stephen A. Ramsey1Maureen K. Larson2Noah E. Berlow3Donasian Ochola4Christopher Shiprack5Amita Kashyap6Bernard Séguin7Charles Keller8Christiane V. Löhr9Department of Biomedical Sciences, Oregon State UniversityDepartment of Biomedical Sciences, Oregon State UniversityDepartment of Clinical Sciences, Oregon State UniversityChildren’s Cancer Therapy Development InstituteFlint Animal Cancer Center, Colorado State UniversityDepartment of Biomedical Sciences, Oregon State UniversityDepartment of Biomedical Sciences, Oregon State UniversityFlint Animal Cancer Center, Colorado State UniversityChildren’s Cancer Therapy Development InstituteDepartment of Biomedical Sciences, Oregon State UniversityAbstract Background Feline injection-site sarcoma (FISS), an aggressive iatrogenic subcutaneous malignancy, is challenging to manage clinically and little is known about the molecular basis of its pathogenesis. Tumor transcriptome profiling has proved valuable for gaining insights into the molecular basis of cancers and for identifying new therapeutic targets. Here, we report the first study of the FISS transcriptome and the first cross-species comparison of the FISS transcriptome with those of anatomically similar soft-tissue sarcomas in dogs and humans. Methods Using high-throughput short-read paired-end sequencing, we comparatively profiled FISS tumors vs. normal tissue samples as well as cultured FISS-derived cell lines vs. skin-derived fibroblasts. We analyzed the mRNA-seq data to compare cancer/normal gene expression level, identify biological processes and molecular pathways that are associated with the pathogenesis of FISS, and identify multimegabase genomic regions of potential somatic copy number alteration (SCNA) in FISS. We additionally conducted cross-species analyses to compare the transcriptome of FISS to those of soft-tissue sarcomas in dogs and humans, at the level of cancer/normal gene expression ratios. Results We found: (1) substantial differential expression biases in feline orthologs of human oncogenes and tumor suppressor genes suggesting conserved functions in FISS; (2) a genomic region with recurrent SCNA in human sarcomas that is syntenic to a feline genomic region of probable SCNA in FISS; and (3) significant overlap of the pattern of transcriptional alterations in FISS with the patterns of transcriptional alterations in soft-tissue sarcomas in humans and in dogs. We demonstrated that a protein, BarH-like homeobox 1 (BARX1), has increased expression in FISS cells at the protein level. We identified 11 drugs and four target proteins as potential new therapies for FISS, and validated that one of them (GSK-1059615) inhibits growth of FISS-derived cells in vitro. Conclusions (1) Window-based analysis of mRNA-seq data can uncover SCNAs. (2) The transcriptome of FISS-derived cells is highly consistent with that of FISS tumors. (3) FISS is highly similar to soft-tissue sarcomas in dogs and humans, at the level of gene expression. This work underscores the potential utility of comparative oncology in improving understanding and treatment of FISS.http://link.springer.com/article/10.1186/s12885-019-5501-zSarcomaComparative oncologymRNA-seqFelineTranscriptome |
| spellingShingle | Qi Wei Stephen A. Ramsey Maureen K. Larson Noah E. Berlow Donasian Ochola Christopher Shiprack Amita Kashyap Bernard Séguin Charles Keller Christiane V. Löhr Elucidating the transcriptional program of feline injection-site sarcoma using a cross-species mRNA-sequencing approach BMC Cancer Sarcoma Comparative oncology mRNA-seq Feline Transcriptome |
| title | Elucidating the transcriptional program of feline injection-site sarcoma using a cross-species mRNA-sequencing approach |
| title_full | Elucidating the transcriptional program of feline injection-site sarcoma using a cross-species mRNA-sequencing approach |
| title_fullStr | Elucidating the transcriptional program of feline injection-site sarcoma using a cross-species mRNA-sequencing approach |
| title_full_unstemmed | Elucidating the transcriptional program of feline injection-site sarcoma using a cross-species mRNA-sequencing approach |
| title_short | Elucidating the transcriptional program of feline injection-site sarcoma using a cross-species mRNA-sequencing approach |
| title_sort | elucidating the transcriptional program of feline injection site sarcoma using a cross species mrna sequencing approach |
| topic | Sarcoma Comparative oncology mRNA-seq Feline Transcriptome |
| url | http://link.springer.com/article/10.1186/s12885-019-5501-z |
| work_keys_str_mv | AT qiwei elucidatingthetranscriptionalprogramoffelineinjectionsitesarcomausingacrossspeciesmrnasequencingapproach AT stephenaramsey elucidatingthetranscriptionalprogramoffelineinjectionsitesarcomausingacrossspeciesmrnasequencingapproach AT maureenklarson elucidatingthetranscriptionalprogramoffelineinjectionsitesarcomausingacrossspeciesmrnasequencingapproach AT noaheberlow elucidatingthetranscriptionalprogramoffelineinjectionsitesarcomausingacrossspeciesmrnasequencingapproach AT donasianochola elucidatingthetranscriptionalprogramoffelineinjectionsitesarcomausingacrossspeciesmrnasequencingapproach AT christophershiprack elucidatingthetranscriptionalprogramoffelineinjectionsitesarcomausingacrossspeciesmrnasequencingapproach AT amitakashyap elucidatingthetranscriptionalprogramoffelineinjectionsitesarcomausingacrossspeciesmrnasequencingapproach AT bernardseguin elucidatingthetranscriptionalprogramoffelineinjectionsitesarcomausingacrossspeciesmrnasequencingapproach AT charleskeller elucidatingthetranscriptionalprogramoffelineinjectionsitesarcomausingacrossspeciesmrnasequencingapproach AT christianevlohr elucidatingthetranscriptionalprogramoffelineinjectionsitesarcomausingacrossspeciesmrnasequencingapproach |