Integrating somatic CNV and gene expression in breast cancers from women with PTEN hamartoma tumor syndrome
Abstract Women with germline PTEN variants (PTEN hamartoma tumor syndrome, PHTS) have up to 85% lifetime risk of female breast cancer (BC). We previously showed that PHTS-derived BCs are distinct from sporadic BCs both at the clinical and genomic levels. In this study, we examined somatic copy numbe...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-07-01
|
| Series: | npj Genomic Medicine |
| Online Access: | https://doi.org/10.1038/s41525-023-00361-0 |
| _version_ | 1797784484092837888 |
|---|---|
| author | Takae Brewer Lamis Yehia Peter Bazeley Charis Eng |
| author_facet | Takae Brewer Lamis Yehia Peter Bazeley Charis Eng |
| author_sort | Takae Brewer |
| collection | DOAJ |
| description | Abstract Women with germline PTEN variants (PTEN hamartoma tumor syndrome, PHTS) have up to 85% lifetime risk of female breast cancer (BC). We previously showed that PHTS-derived BCs are distinct from sporadic BCs both at the clinical and genomic levels. In this study, we examined somatic copy number variations (CNV) and transcriptome data to further characterize the somatic landscape of PHTS-derived BCs. We analyzed exome sequencing data from 44 BCs from women with PHTS for CNV. The control group comprised of 558 women with sporadic BCs from The Cancer Genome Atlas (TCGA) dataset. Here, we found that PHTS-derived BCs have several distinct CNV peaks compared to TCGA. Furthermore, RNA sequencing data revealed that PHTS-derived BCs have a distinct immunologic cell type signature, which points toward cancer immune evasion. Transcriptomic data also revealed PHTS-derived BCs with pathogenic germline PTEN variants appear to have vitamin E degradation as a key pathway associated with tumorigenesis. In conclusion, our study revealed distinct CNV x transcript features in PHTS-derived BCs, which further facilitate understanding of BC biology arising in the setting of germline PTEN mutations. |
| first_indexed | 2024-03-13T00:40:33Z |
| format | Article |
| id | doaj.art-5440b66ccc45435e80153901127bc4d1 |
| institution | Directory Open Access Journal |
| issn | 2056-7944 |
| language | English |
| last_indexed | 2024-03-13T00:40:33Z |
| publishDate | 2023-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Genomic Medicine |
| spelling | doaj.art-5440b66ccc45435e80153901127bc4d12023-07-09T11:20:09ZengNature Portfolionpj Genomic Medicine2056-79442023-07-018111010.1038/s41525-023-00361-0Integrating somatic CNV and gene expression in breast cancers from women with PTEN hamartoma tumor syndromeTakae Brewer0Lamis Yehia1Peter Bazeley2Charis Eng3Genomic Medicine Institute, Lerner Research Institute, Cleveland ClinicGenomic Medicine Institute, Lerner Research Institute, Cleveland ClinicDepartment of Quantitative Health Sciences, Lerner Research Institute, Cleveland ClinicGenomic Medicine Institute, Lerner Research Institute, Cleveland ClinicAbstract Women with germline PTEN variants (PTEN hamartoma tumor syndrome, PHTS) have up to 85% lifetime risk of female breast cancer (BC). We previously showed that PHTS-derived BCs are distinct from sporadic BCs both at the clinical and genomic levels. In this study, we examined somatic copy number variations (CNV) and transcriptome data to further characterize the somatic landscape of PHTS-derived BCs. We analyzed exome sequencing data from 44 BCs from women with PHTS for CNV. The control group comprised of 558 women with sporadic BCs from The Cancer Genome Atlas (TCGA) dataset. Here, we found that PHTS-derived BCs have several distinct CNV peaks compared to TCGA. Furthermore, RNA sequencing data revealed that PHTS-derived BCs have a distinct immunologic cell type signature, which points toward cancer immune evasion. Transcriptomic data also revealed PHTS-derived BCs with pathogenic germline PTEN variants appear to have vitamin E degradation as a key pathway associated with tumorigenesis. In conclusion, our study revealed distinct CNV x transcript features in PHTS-derived BCs, which further facilitate understanding of BC biology arising in the setting of germline PTEN mutations.https://doi.org/10.1038/s41525-023-00361-0 |
| spellingShingle | Takae Brewer Lamis Yehia Peter Bazeley Charis Eng Integrating somatic CNV and gene expression in breast cancers from women with PTEN hamartoma tumor syndrome npj Genomic Medicine |
| title | Integrating somatic CNV and gene expression in breast cancers from women with PTEN hamartoma tumor syndrome |
| title_full | Integrating somatic CNV and gene expression in breast cancers from women with PTEN hamartoma tumor syndrome |
| title_fullStr | Integrating somatic CNV and gene expression in breast cancers from women with PTEN hamartoma tumor syndrome |
| title_full_unstemmed | Integrating somatic CNV and gene expression in breast cancers from women with PTEN hamartoma tumor syndrome |
| title_short | Integrating somatic CNV and gene expression in breast cancers from women with PTEN hamartoma tumor syndrome |
| title_sort | integrating somatic cnv and gene expression in breast cancers from women with pten hamartoma tumor syndrome |
| url | https://doi.org/10.1038/s41525-023-00361-0 |
| work_keys_str_mv | AT takaebrewer integratingsomaticcnvandgeneexpressioninbreastcancersfromwomenwithptenhamartomatumorsyndrome AT lamisyehia integratingsomaticcnvandgeneexpressioninbreastcancersfromwomenwithptenhamartomatumorsyndrome AT peterbazeley integratingsomaticcnvandgeneexpressioninbreastcancersfromwomenwithptenhamartomatumorsyndrome AT chariseng integratingsomaticcnvandgeneexpressioninbreastcancersfromwomenwithptenhamartomatumorsyndrome |