ArticlePloS one2014
Whole genome sequence analysis suggests intratumoral heterogeneity in dissemination of breast cancer to lymph nodes.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 19 citations in OpenAlex.
- Genomic analysis of germ line and somatic variants in familial myelodysplasia/acute myeloid leukemia.Blood · 2015Trial
- Role of intratumoral heterogeneity in metastatic progression and drug resistance.Discover oncology · 2025Review
- Review
- Fixing the GAP: The role of RhoGAPs in cancer.European journal of cell biology · 2022Review
- PDS5B inhibits cell proliferation, migration, and invasion via upregulation of LATS1 in lung cancer cells.Cell death discovery · 2021Article
- The sick lobe hypothesis, field cancerisation and the new era of precision breast surgery.Gland surgery · 2018Review
- Lymph Nodes in Breast Cancer - What Can We Learn from Translational Research?Breast care (Basel, Switzerland) · 2018Review
- Breast carcinoma subtypes show different patterns of metastatic behavior.Virchows Archiv : an international journal of pathology · 2017Article
- The human, F-actin-based cytoskeleton as a mutagen sensor.Cancer cell international · 2017Article
- Suppressive Role of MicroRNA-148a in Cell Proliferation and Invasion in Ovarian Cancer Through Targeting Transforming Growth Factor-β-Induced 2.Oncology research · 2016Article
- Turning the headlights on novel cancer biomarkers: Inspection of mechanics underlying intratumor heterogeneity.Molecular aspects of medicine · 2015Review
- The role of individual inheritance in tumor progression and metastasis.Journal of molecular medicine (Berlin, Germany) · 2015Review
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundIntratumoral heterogeneity may help drive resistance to targeted therapies in cancer. In breast cancer, the presence of nodal metastases is a key indicator of poorer overall survival. The aim of this study was to identify somatic genetic alterations in early dissemination of breast cancer by whole genome next generation sequencing (NGS) of a primary breast tumor, a matched locally-involved axillary lymph node and healthy normal DNA from blood.
methodsWhole genome NGS was performed on 12 µg (range 11.1-13.3 µg) of DNA isolated from fresh-frozen primary breast tumor, axillary lymph node and peripheral blood following the DNA nanoball sequencing protocol. Single nucleotide variants, insertions, deletions, and substitutions were identified through a bioinformatic pipeline and compared to CIN25, a key set of genes associated with tumor metastasis.
resultsWhole genome sequencing revealed overlapping variants between the tumor and node, but also variants that were unique to each. Novel mutations unique to the node included those found in two CIN25 targets, TGIF2 and CCNB2, which are related to transcription cyclin activity and chromosomal stability, respectively, and a unique frameshift in PDS5B, which is required for accurate sister chromatid segregation during cell division. We also identified dominant clonal variants that progressed from tumor to node, including SNVs in TP53 and ARAP3, which mediates rearrangements to the cytoskeleton and cell shape, and an insertion in TOP2A, the expression of which is significantly associated with tumor proliferation and can segregate breast cancers by outcome.
conclusionThis case study provides preliminary evidence that primary tumor and early nodal metastasis have largely overlapping somatic genetic alterations. There were very few mutations unique to the involved node. However, significant conclusions regarding early dissemination needs analysis of a larger number of patient samples.
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