The Polemic Diagnostic Role of TP53 Mutations in Liquid Biopsies from Breast, Colon and Lung Cancers

Garrido-Navas, M. Carmen; Garcia-Diaz, A.; Molina-Vallejo, Maria Pilar; González-Martínez, Coral; Lucena, M Alcaide; Cañas-García, Inés; Bayarri, Clara; Delgado, Juan Ramón; González, Elena Navarro; Lorente, José A.; Serrano, María José

doi:10.3390/cancers12113343

“…Approximately, 19.1% of patients carried TP53 mutations are in accordance with the previous studies, which reported the frequency of somatic TP53 mutations ranging from 15% to 71%. Somatic TP53 mutation leads to disruption in the cell cycle, induced apoptosis, and affected DNA damage repair process, and the presence of TP53 mutations in cfDNA was associated with lower PFS independently of clinical treatment [ 18 ]. Approximately 17.6% of patients carried PIK3CA mutations.…”

Section: Discussionmentioning

confidence: 99%

“…Gene mutations in cfDNA have shown some prognostic significance, and these mutations can be detected in plasma cfDNA by next generation sequencing (NGS) [ 1 ]. There is a clear correlation between presence of TP53 mutations in cfDNA and adverse progression-free survival (PFS) outcome [ 18 ]. Several retrospective studies have also reported that ESR1 or PIK3CA mutations were related to shorter PFS and overall survival (OS) in hormone receptor- (HR-) positive metastatic BC [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

Cell-Free DNA Variables including Gene Mutations in CA15-3 Normal Breast Cancer Reflect Prognosis

Xu

¹

,

Chen

²

,

Sun

³

et al. 2022

Disease Markers

0

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Background. Cell-free DNA (cfDNA) has attracted considerable attention in precision medicine. However, few data are available regarding to the prognostic value of cfDNA variables in CA15-3 normal breast cancer (BC) patients. Here, we aimed at investigating the prognostic value of cfDNA variables including gene mutations in CA15-3 normal BC patients. Methods. A total of 68 BC patients with normal CA15-3 levels were enrolled. cfDNA concentration and integrity were assessed based on qPCR. cfDNA gene mutations were conducted by using next gene sequencing (NGS). The association between cfDNA variables and the prognosis of patients was analyzed. Results. cfDNA concentration was related to tumor stage ( P = 0.002 ), metastases ( P = 0.001 ), and distant metastases ( P < 0.001 ). The elevated copy number variants (CNV) were found in distant metastasis patients compared with patients without distant metastases ( P = 0.008 ). Nineteen mutant genes were validated in enrolled CA15-3 normal BC patients. Thirty-two patients (47.0%) had single nucleotide variants (SNV), and 13 (19.1%) patients had TP53 mutations (TP53mut). SNV ( P = 0.033 ) was related to tumor stage, and TP53mut was related to metastases ( P = 0.016 ) and distant metastases ( P = 0.006 ). In multivariate logistic analysis, cfDNA concentration was associated with metastases ( OR = 3.404 , 95% CI: 1.074-10.788, P = 0.037 ) and distant metastases ( OR = 13.750 , 95% CI: 1.473-128.358, P = 0.021 ). Cases with high cfDNA levels (>15.6 ng/ml), SNV, and TP53mut showed worse DFS compared with patients with low cfDNA levels ( P < 0.001 ), without SNV ( P = 0.002 ) and with TP53 wildtype ( P < 0.001 ), respectively. In the multivariate Cox proportional hazard model, cfDNA concentration was an independent predictor of poor survival ( HR = 5.786 , 95% CI: 1.101-30.407, P = 0.038 ). Conclusions. Assessment of cfDNA concentration, CNV, SNV, and TP53mut could be useful in predicting prognosis for CA15-3 normal BC patients. The cfDNA concentration was an independent predictor prognostic factor in CA15-3 normal BC patients.

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“…The rate of TP53 mutation frequency in cfDNA varies from 31% to about 50% across studies [ 141 , 142 ]. On the other hand, the reported VAF of TP53 mutations in plasma have a broader variation than mutation rate, ranging from 0.09% to 70% across different reports [ 143 ]. A meta-analysis which reported a mutation rate of 37.8% for TP53 in cfDNA independent of tumor stage indicated that TP53 mutations were associated with recurrence, short disease-free survival (DFS), and PFS.…”

Section: Use Of Digital Pcr In Ctdna Analysis In Breast Cancer Patientsmentioning

confidence: 99%

The Clinical Utility of Droplet Digital PCR for Profiling Circulating Tumor DNA in Breast Cancer Patients

Gezer

¹

,

Bronkhorst

²

,

Holdenrieder

³

2022

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Breast cancer is the most common cancer affecting women worldwide. It is a malignant and heterogeneous disease with distinct molecular subtypes, which has prognostic and predictive implications. Circulating tumor DNA (ctDNA), cell-free fragmented tumor-derived DNA in blood plasma, is an invaluable source of specific cancer-associated mutations and holds great promise for the development of minimally invasive diagnostic tests. Furthermore, serial monitoring of ctDNA over the course of systemic and targeted therapies not only allows unparalleled efficacy assessments but also enables the identification of patients who are at risk of progression or recurrence. Droplet digital PCR (ddPCR) is a powerful technique for the detection and monitoring of ctDNA. Due to its relatively high accuracy, sensitivity, reproducibility, and capacity for absolute quantification, it is increasingly used as a tool for managing cancer patients through liquid biopsies. In this review paper, we gauge the clinical utility of ddPCR as a technique for mutational profiling in breast cancer patients and focus on HER2, PIK3CA, ESR1, and TP53, which represent the most frequently mutated genes in breast cancers.

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“…This mechanism of neoplastic transformation mediated by ctDNA has been proved in fibroblastic cell cultures [ 86 ] or CRC and pancreatic-cell-line models [ 87 , 88 ]. It was also assumed that distant metastases in CRC may be formed as a result of the transfection of normal cells located in the target organs, with ctDNA harboring mutations in the TP53 , KRAS , and HBB genes [ 89 , 90 ]. Furthermore, CRC-derived ctDNA increased, in vitro, the expression of the mRNA level of 118 genes, which included genes with metastatic potentials, such as INSIG1 , CREB3L2 , CEACAM5 , LIPG , or DAPP1 [ 91 ].…”

Section: Role Of Ctcs and Ctdna In Metastatic Spreadmentioning

confidence: 99%

The Overview of Perspectives of Clinical Application of Liquid Biopsy in Non-Small-Cell Lung Cancer

Bożyk

¹

,

Nicoś

²

2022

Life

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The standard diagnostics procedure for non-small-cell lung cancer (NSCLC) requires a pathological evaluation of tissue samples obtained by surgery or biopsy, which are considered invasive sampling procedures. Due to this fact, re-sampling of the primary tumor at the moment of progression is limited and depends on the patient’s condition, even if it could reveal a mechanism of resistance to applied therapy. Recently, many studies have indicated that liquid biopsy could be provided for the noninvasive management of NSCLC patients who receive molecularly targeted therapies or immunotherapy. The liquid biopsy of neoplastic patients harbors small fragments of circulating-free DNA (cfDNA) and cell-free RNA (cfRNA) secreted to the circulation from normal cells, as well as a subset of tumor-derived circulating tumor cells (CTCs) or circulating tumor DNA (ctDNA). In NSCLC patients, a longitudinal assessment of genetic alterations in “druggable” genes in liquid biopsy might improve the follow-up of treatment efficacy and allow for the detection of an early progression before it is detectable in computed tomography or a clinical image. However, a liquid biopsy may be used to determine a variety of relevant molecular or genetic information for understanding tumor biology and its evolutionary trajectories. Thus, liquid biopsy is currently associated with greater hope for common diagnostic and clinical applications. In this review, we would like to highlight diagnostic challenges in the application of liquid biopsy into the clinical routine and indicate its implications on the metastatic spread of NSCLC or monitoring of personalized treatment regimens.

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The Polemic Diagnostic Role of TP53 Mutations in Liquid Biopsies from Breast, Colon and Lung Cancers

Cited by 14 publications

References 100 publications

Cell-Free DNA Variables including Gene Mutations in CA15-3 Normal Breast Cancer Reflect Prognosis

Cell-Free DNA Variables including Gene Mutations in CA15-3 Normal Breast Cancer Reflect Prognosis

The Clinical Utility of Droplet Digital PCR for Profiling Circulating Tumor DNA in Breast Cancer Patients

The Overview of Perspectives of Clinical Application of Liquid Biopsy in Non-Small-Cell Lung Cancer

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