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pmid:35932380

Comparative analysis of the molecular subtype landscape in canine and human mammary gland tumors.

Helga Bergholtz · Tonje Lien · Frode Lingaas · Therese Sørlie

Journal of mammary gland biology and neoplasia · 2022 doi:10.1007/s10911-022-09523-9

Paper

complete

Experiment

complete

Data

partial

Analysis

partial

Execution

absent

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title
Comparative analysis of the molecular subtype landscape in canine and human mammary gland tumors.
doi
10.1007/s10911-022-09523-9
pmid
35932380
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[0]
Helga Bergholtz
[1]
Tonje Lien
[2]
Frode Lingaas
[3]
Therese Sørlie
journal
Journal of mammary gland biology and neoplasia
year
2022
abstract
Breast cancers in humans belong to one of several intrinsic molecular subtypes each with different tumor biology and different clinical impact. Mammary gland tumors in dogs are proposed as a relevant comparative model for human breast cancer; however, it is still unclear whether the intrinsic molecular subtypes have the same significance in dogs and humans. Using publicly available data, we analyzed gene expression and whole-exome sequencing data from 158 canine mammary gland tumors. We performed molecular subtyping using the PAM50 method followed by subtype-specific comparisons of gene expression characteristics, mutation patterns and copy number profiles between canine tumors and human breast tumors from The Cancer Genome Atlas (TCGA) breast cancer cohort (n = 1097). We found that luminal A canine tumors greatly resemble luminal A human tumors both in gene expression characteristics, mutations and copy number profiles. Also, the basal-like canine and human tumors were relatively similar, with low expression of luminal epithelial markers and high expression of genes involved in cell proliferation. There were, however, distinct differences in immune-related gene expression patterns in basal-like tumors between the two species. Characteristic HER2-enriched and luminal B subtypes were not present in the canine cohort, and we found no tumors with high-level ERBB2 amplifications. Benign and malignant canine tumors displayed similar PAM50 subtype characteristics. Our findings indicate that deeper understanding of the different molecular subtypes in canine mammary gland tumors will further improve the value of canines as comparative models for human breast cancer.
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Among the canine tumors, there was a significantly different distribution of tumors with PIK3CA and TP53 mutations between the subtypes (Fisher’s Exact Test, p-values: PIK3CA = 0.04, TP53 < 0.001) with more PIK3CA mutations in luminal tumors and more TP53 mutations in basal-like tumors (Fig. 3c).
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sections[22] "Similar Association Between Subtype and PIK3CA and TP53 Mutations" paragraph 3
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Among the canine tumors, there was a significantly different distribution of tumors with PIK3CA and TP53 mutations between the subtypes (Fisher’s Exact Test, p-values: PIK3CA = 0.04, TP53 < 0.001) with more PIK3CA mutations in luminal tumors and more TP53 mutations in basal-like tumors (Fig. 3c).
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Data used in this study are publicly available. The gene expression data can be accessed from the NCBI GEO database under accession number GSE119810 [26]. Clinical information and variant calling data can be downloaded from https://doi.org/10.6084/m9.figshare.c.4543784.v1. Raw data are available from the Sequence Read Archive IDs (SRP159466 and SRP159481) [74, 75].
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Data used in this study are publicly available. The gene expression data can be accessed from the NCBI GEO database under accession number GSE119810 [26]. Clinical information and variant calling data can be downloaded from https://doi.org/10.6084/m9.figshare.c.4543784.v1. Raw data are available from the Sequence Read Archive IDs (SRP159466 and SRP159481) [74, 75].
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PIK3CA mutations were more common in luminal tumors and TP53 mutations were more common in basal-like tumors in both canine and human breast tumors.
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sections[22] "Similar Association Between Subtype and PIK3CA and TP53 Mutations" paragraph 3
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Among the canine tumors, there was a significantly different distribution of tumors with PIK3CA and TP53 mutations between the subtypes (Fisher’s Exact Test, p-values: PIK3CA = 0.04, TP53 < 0.001) with more PIK3CA mutations in luminal tumors and more TP53 mutations in basal-like tumors (Fig. 3c).
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The same pattern is found in human tumors (Fisher’s Exact Test, p-values: PIK3CA < 0.001, TP53 < 0.001) [28].
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PIK3CA mutations were more common in luminal tumors and TP53 mutations were more common in basal-like tumors in both canine and human breast tumors.
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Among the canine tumors, there was a significantly different distribution of tumors with PIK3CA and TP53 mutations between the subtypes (Fisher’s Exact Test, p-values: PIK3CA = 0.04, TP53 < 0.001) with more PIK3CA mutations in luminal tumors and more TP53 mutations in basal-like tumors (Fig. 3c).
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Data used in this study are publicly available. The gene expression data can be accessed from the NCBI GEO database under accession number GSE119810 [26]. Clinical information and variant calling data can be downloaded from https://doi.org/10.6084/m9.figshare.c.4543784.v1. Raw data are available from the Sequence Read Archive IDs (SRP159466 and SRP159481) [74, 75].
basis
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Mammary gland tumors in dogs are proposed as a relevant comparative model for human breast cancer; however, it is still unclear whether the intrinsic molecular subtypes have the same significance in dogs and humans. Using publicly available data, we analyzed gene expression and whole-exome sequencing data from 158 canine mammary gland tumors. We performed molecular subtyping using the PAM50 method followed by subtype-specific comparisons of gene expression characteristics, mutation patterns and copy number profiles between canine tumors and human breast tumors from The Cancer Genome Atlas (TCGA) breast cancer cohort (n = 1097). We found that luminal A canine tumors greatly resemble luminal A human tumors both in gene expression characteristics, mutations and copy number profiles. Also, the basal-like canine and human tumors were relatively similar, with low expression of luminal epithelial markers and high expression of genes involved in cell proliferation. There were, however, distinct differences in immune-related gene expression patterns in basal-like tumors between the two species. Characteristic HER2-enriched and luminal B subtypes were not present in the canine cohort, and we found no tumors with high-level ERBB2 amplifications. Benign and malignant canine tumors displayed similar PAM50 subtype characteristics. 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