+ Site Statistics
References:
54,258,434
Abstracts:
29,560,870
PMIDs:
28,072,757
+ Search Articles
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ PDF Full Text
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Translate
+ Recently Requested

TP53 mutations detected in circulating tumor cells present in the blood of metastatic triple negative breast cancer patients



TP53 mutations detected in circulating tumor cells present in the blood of metastatic triple negative breast cancer patients



Breast Cancer Research 16(5): 445



Circulating tumor cells (CTCs) are tumor cells shed from either primary tumors or its metastases that circulate in the peripheral blood of patients with metastatic cancers. The molecular characterization of the CTCs is critical to identifying the key drivers of cancer metastasis and devising therapeutic approaches. However, the molecular characterization of CTCs is difficult to achieve because their isolation is a major technological challenge. CTCs from two triple negative breast cancer patients were enriched using CellSearch and single cells selected by DEPArray™. A TP53 R110 fs*13 mutation identified by next generation sequencing in the breast and chest skin biopsies of both patients was studied in single CTCs. From 6 single CTC isolated from one patient, 1 CTC had TP53 R110 delC, 1 CTC showed the TP53 R110 delG mutation, and the remaining 4 single CTCs showed the wild type p53 sequence; a pool of 14 CTCs isolated from the same patient also showed TP53 R110 delC mutation. In the tumor breast tissue of this patient, only the TP53 R110 delG mutation was detected. In the second patient a TP53 R110 delC mutation was detected in the chest wall skin biopsy; from the peripheral blood of this patient, 5 single CTC and 6 clusters of 2 to 6 CTCs were isolated; 3 of the 5 single CTCs showed the TP53 R110 delC mutation and 2 CTCs showed the wild type TP53 allele; from the clusters, 5 showed the TP53 R110 delC mutation, and 1 cluster the wild type TP53 allele. Single white blood cells isolated as controls from both patients only showed the wild type TP53 allele. We are able to isolate uncontaminated CTCs and achieve single cell molecular analysis. Our studies showed the presence of different CTC sub-clones in patients with metastatic breast cancer. Some CTCs had the same TP53 mutation as their matching tumor samples although others showed either a different TP53 mutation or the wild type allele. Our results indicate that CTCs could represent a non-invasive source of cancer cells from which to determine genetic markers of the disease progression and potential therapeutic targets.

(PDF emailed within 0-6 h: $19.90)

Accession: 056105979

Download citation: RISBibTeXText

PMID: 25307991

DOI: 10.1186/s13058-014-0445-3


Related references

Circulating tumor DNA and circulating tumor cells in metastatic triple negative breast cancer patients. International Journal of Cancer 136(9): 2158-2165, 2015

Significance of Circulating Tumor Cells in Metastatic Triple-Negative Breast Cancer Patients within a Randomized, Phase II Trial: TBCRC 019. Clinical Cancer Research 21(12): 2771-2779, 2016

Circulating tumor cells (CTCs) detected by triple-marker EpCAM, CK19, and hMAM RT-PCR and their relation to clinical outcome in metastatic breast cancer patients. Cell Biochemistry and Biophysics 65(2): 263-273, 2013

Circulating tumor cells in non-metastatic triple-negative breast cancer. Breast Cancer Research and Treatment 147(2): 325-333, 2015

Frequent detection of PIK3CA mutations in single circulating tumor cells of patients suffering from HER2-negative metastatic breast cancer. Molecular Oncology 10(8): 1330-1343, 2017

Circulating Tumor Cells Detected by RT-PCR for CK-20 before Surgery Indicate Worse Prognostic Impact in Triple-Negative and HER2 Subtype Breast Cancer. Journal of Breast Cancer 15(1): 34-42, 2012

Circulating tumor cells predict progression-free and overall survival in Chinese patients with metastatic breast cancer, HER2-positive or triple-negative (CBCSG004): a multicenter, double-blind, prospective trial. Annals of Oncology 24(11): 2766-2772, 2014

A Cross-Sectional Comparison of Druggable Mutations in Primary Tumors, Metastatic Tissue, Circulating Tumor Cells, and Cell-Free Circulating DNA in Patients with Metastatic Breast Cancer: The MIRROR Study Protocol. Jmir Research Protocols 5(3): E167, 2016

Microglandular adenosis associated with triple-negative breast cancer is a neoplastic lesion of triple-negative phenotype harbouring TP53 somatic mutations. Journal of Pathology 238(5): 677-688, 2016

Circulating tumor cells and bone metastases as detected by FDG-PET/CT in patients with metastatic breast cancer. Annals of Oncology 21(1): 33-39, 2010

Phenotypic characterization of circulating tumor cells in triple negative breast cancer patients. Oncotarget 8(3): 5309-5322, 2016

Circulating Tumor DNA Guides Prognosis in Metastatic Triple-Negative Breast Cancer. Journal of Clinical Oncology 36(6): 523-524, 2018

Analysis of circulating tumor cells in patients with triple negative breast cancer during preoperative chemotherapy. Bulletin of Experimental Biology and Medicine 157(1): 159-161, 2015

Prognostic relevance of viable circulating tumor cells detected by EPISPOT in metastatic breast cancer patients. Clinical Chemistry 60(1): 214-221, 2014

Significance of Circulating Tumor Cells Detected by the CellSearch System in Patients with Metastatic Breast Colorectal and Prostate Cancer. Journal of Oncology 2010: 617421, 2009