Intratumoral genomic heterogeneity, or ITGH, refers to the genetic and functional differences that can exist within different regions of a single tumor. These differences often explain why some cancers resist therapy. A team led by researchers at the Roswell Park Comprehensive Cancer Center and the University of Buffalo explored whether a tool called the DEPTH2 algorithm can estimate this heterogeneity using only RNA expression data, rather than requiring both DNA and RNA information.
To understand how well DEPTH2 performs, the team analyzed data from 7508 breast cancer patients across several large cohorts. Patients with high DEPTH2 scores tended to have worse overall survival in the SCAN-B cohort. However, this link did not appear in the TCGA or METABRIC cohorts, showing that DEPTH2 might work differently depending on the dataset.
Genomic characteristics of breast cancer patients by DEPTH2 score
(A) Correlation plot of ITGH assessed by ABSOLUTE algorithm, as well as homologous recombination defects (HRDs), copy number alteration (CNA), silent and non-silent mutation rates, and single-nucleotide variant (SNV) and insert and deletion (Indel) neoantigens between high and low ITGH breast cancer.
High scores were associated with increased cancer cell growth. These patients showed higher tumor grades, elevated Ki67 gene expression, and strong enrichment of gene sets tied to cell proliferation. Tumors with higher scores also had more immune cell infiltration, which indicates a more biologically active tumor environment.
Among breast cancer subtypes, triple negative breast cancer had the highest DEPTH2 scores, yet these higher values did not align with the presence of lymph node or distant metastases. When looking at the effects of neoadjuvant chemotherapy, DEPTH2 scores decreased in two patient cohorts but remained unchanged in two others. In addition, the score did not predict which patients would achieve a complete response to chemotherapy.
Taken together, the findings suggest that while DEPTH2 reflects important features like tumor growth and immune involvement, it may not capture all aspects of tumor heterogeneity in breast cancer or reliably predict treatment outcomes.
Chida K, Wu R, Roy AM, Ishikawa T, Hakamada K, Takabe K. (2025) DEPTH2 score was associated with cell proliferation and immune cell infiltrations but not with systemic treatment response in breast cancer. Sci Rep 15(1):42225. [article]
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Intratumoral genomic heterogeneity, or ITGH, refers to the genetic and functional differences that can exist within different regions of a single tumor. These differences often explain why some cancers resist therapy. A team led by researchers at the Roswell Park Comprehensive Cancer Center and the University of Buffalo explored whether a tool called the DEPTH2 algorithm can estimate this heterogeneity using only RNA expression data, rather than requiring both DNA and RNA information.
To understand how well DEPTH2 performs, the team analyzed data from 7508 breast cancer patients across several large cohorts. Patients with high DEPTH2 scores tended to have worse overall survival in the SCAN-B cohort. However, this link did not appear in the TCGA or METABRIC cohorts, showing that DEPTH2 might work differently depending on the dataset.
Genomic characteristics of breast cancer patients by DEPTH2 score
(A) Correlation plot of ITGH assessed by ABSOLUTE algorithm, as well as homologous recombination defects (HRDs), copy number alteration (CNA), silent and non-silent mutation rates, and single-nucleotide variant (SNV) and insert and deletion (Indel) neoantigens between high and low ITGH breast cancer.
High scores were associated with increased cancer cell growth. These patients showed higher tumor grades, elevated Ki67 gene expression, and strong enrichment of gene sets tied to cell proliferation. Tumors with higher scores also had more immune cell infiltration, which indicates a more biologically active tumor environment.
Among breast cancer subtypes, triple negative breast cancer had the highest DEPTH2 scores, yet these higher values did not align with the presence of lymph node or distant metastases. When looking at the effects of neoadjuvant chemotherapy, DEPTH2 scores decreased in two patient cohorts but remained unchanged in two others. In addition, the score did not predict which patients would achieve a complete response to chemotherapy.
Taken together, the findings suggest that while DEPTH2 reflects important features like tumor growth and immune involvement, it may not capture all aspects of tumor heterogeneity in breast cancer or reliably predict treatment outcomes.
Chida K, Wu R, Roy AM, Ishikawa T, Hakamada K, Takabe K. (2025) DEPTH2 score was associated with cell proliferation and immune cell infiltrations but not with systemic treatment response in breast cancer. Sci Rep 15(1):42225. [article]
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