Genotyping tumour DNA in cerebrospinal fluid and plasma of a HER2-positive breast cancer patient with brain metastases

Siravegna, Giulia; Geuna, Elena; Mussolin, Benedetta; Crisafulli, Giovanni; Bartolini, Alice; Galizia, Danilo; Casorzo, Laura; Sarotto, Ivana; Scaltriti, Maurizio; Sapino, Anna; Bardelli, Alberto; Montemurro, Filippo

doi:10.1136/esmoopen-2017-000253

Cited by 56 publications

(48 citation statements)

References 11 publications

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“…Their results indicated an increase in TP53 , PIK3CA , ERBB2 , and cMYC alterations in ctDNA extracted from CSF, while plasma ctDNA was decreased post‐treatment. The results of this study were indicative of better response to treatment of breast cancer metastasis outside of CNS compared to CNS metastasis …”

Section: Liquid Biopsy Componentsmentioning

confidence: 72%

Liquid biopsy in breast cancer: A comprehensive review

2019

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Breast cancer is the most common cancer among women worldwide. Due to its complexity in nature, effective breast cancer treatment can encounter many challenges. Traditional methods of cancer detection such as tissue biopsy are not comprehensive enough to capture the entire genomic landscape of breast tumors. However, with the introduction of novel techniques, the application of liquid biopsy has been enhanced, enabling the improvement of various aspects of breast cancer management including early diagnosis and screening, prediction of prognosis, early detection of relapse, serial sampling and efficient longitudinal monitoring of disease progress and response to treatment. Various components of tumor cells released into the blood circulation can be analyzed in liquid biopsy sampling, some of which include circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), cell‐free RNA, tumor‐educated platelets and exosomes. These components can be utilized for different purposes. As an example, ctDNA can be sequenced for genetic profiling of the tumors to enhance individualized treatment and longitudinal screening. CTC plasma count analysis or ctDNA detection after curative tumor resection surgery could facilitate early detection of minimal residual disease, aiding in the initiation of adjuvant therapy to prevent recurrence. Furthermore, CTC plasma count can be assessed to determine the stage and prognosis of breast cancer. In this review, we discuss the advantages and limitations of the various components of liquid biopsy used in breast cancer diagnosis and will expand on aspects that require further focus in future research.

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Section: Liquid Biopsy Componentsmentioning

confidence: 72%

Liquid biopsy in breast cancer: A comprehensive review

2019

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“…Although less cell‐free DNA (CFDNA) is captured from the CSF compared with the plasma, the CFDNA in the CSF is predominantly tumor‐derived. CSF ctDNA may also be subjected to a number of sequencing approaches, including digital PCR, targeted exome sequencing, whole exome, and other evolving technologies (De Mattos‐Arruda et al, ; Fan et al, ; Li et al, ; Marchio et al, ; Momtaz et al, ; Siravegna, Geuna, et al, ; Siravegna, Marsoni, Siena, & Bardelli, ).…”

Section: Circulating Tumor Cells and Cell‐free Dnamentioning

confidence: 99%

Leptomeningeal disease in melanoma patients: An update to treatment, challenges, and future directions

Glitza

Smalley

Brastianos

et al. 2020

Pigment Cell Melanoma Res

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In February 2018, the Melanoma Research Foundation and the Moffitt Cancer Center hosted the Second Summit on Melanoma Central Nervous System Metastases in Tampa, Florida. The meeting included investigators from multiple academic centers and disciplines. A consensus summary of the progress and challenges in melanoma parenchymal brain metastases was published (Eroglu et al., Pigment Cell & Melanoma Research, 2019, 32, 458). Here, we will describe the current state of basic, translational, clinical research, and therapeutic management, for melanoma patients with leptomeningeal disease. We also outline key challenges and barriers to be overcome to make progress in this deadly disease.

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“…Therefore, in this study, we aimed to compare the results from CSF ctDNA with plasma ctDNA, plasma CTCs, and brain tissue specimens in patients with brain metastasis from NSCLC. The assessment of CSF ctDNA could provide a snapshot of what actually occurs in brain metastases, to more precisely guide therapy . Sequencing of CSF ctDNA revealed specific mutation patterns in driver genes among patients with NSCLC and brain metastases.…”

Section: Discussionmentioning

confidence: 99%

“…The assessment of CSF ctDNA could provide a snapshot of what actually occurs in brain metastases, 11,15 to more precisely guide therapy. [16][17][18] Sequencing of CSF ctDNA revealed specific mutation patterns in driver genes among patients with NSCLC and brain metastases. This is the first study comparing CSF ctDNA, blood ctDNA, CTCs, and brain tissue in patients with NSCLC and brain metastases.…”

Section: Discussionmentioning

confidence: 99%

Detection of circulating tumor DNA from non‐small cell lung cancer brain metastasis in cerebrospinal fluid samples

Yang

Xing

et al. 2020

Thoracic Cancer

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Background Evaluating the molecular characteristics of brain metastases is limited by difficult access and by the blood–brain barrier, which prevents circulating tumor DNA (ctDNA) from entering the blood. In this study, we aimed to compare the sequencing results from cerebrospinal fluid (CSF) ctDNA versus plasma ctDNA, plasma circulating tumor cells (CTCs), and brain tissue specimens from patients with brain metastasis from non‐small cell lung cancer (NSCLC). Methods This was a prospective study of 21 consecutive patients with NSCLC and brain metastasis diagnosed between April 2018 and January 2019. Samples of CSF and peripheral blood were obtained from all 21 patients. Brain tissues were obtained from five patients after surgical resection. Next‐generation sequencing was performed using the Ion system. Single nucleotide variants (SNVs) and small insertions or deletions (indels) were searched. Results Mutations were detected in the CSF ctDNA of 20 (95.2%) patients. The detection rate of epidermal growth factor receptor (EGFR) mutations in CSF ctDNA was 57.1% (12/21) whereas this rate was only 23.8% (5/21) in peripheral blood ctDNA and in CTCs. EGFR mutations were found in the CSF of 9 of 11 (81.8%) patients with leptomeningeal metastases, as compared with three of 10 (30%) patients with brain parenchymal metastases. Mutations were also detected in KIT, PIK3CA, TP53, SMAD4, ATM, SMARCB1, PTEN, FLT3, GNAS, STK11, MET, CTNNB1, APC, FBXW7, ERBB4, and KDR (all >10%). The status of EGFR and TP53 mutations was consistent between CSF ctDNA and brain lesion tissue in all five patients. Conclusion Sequencing of CSF ctDNA revealed specific mutation patterns in driver genes among patients with NSCLC and brain metastasis. Key points In some small‐sample studies, the importance of cerebrospinal fluid in guiding the treatment of cancerous brain lesions has been verified in that it may reflect genomic mutations of brain tumors relatively accurately. Cerebrospinal fluid is a new form of liquid biopsy that can be helpful in improving the management of patients with brain metastasis from non‐small cell lung cancer by detecting genetic abnormalities specific to brain metastases.

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Genotyping tumour DNA in cerebrospinal fluid and plasma of a HER2-positive breast cancer patient with brain metastases

Cited by 56 publications

References 11 publications

Liquid biopsy in breast cancer: A comprehensive review

Liquid biopsy in breast cancer: A comprehensive review

Leptomeningeal disease in melanoma patients: An update to treatment, challenges, and future directions

Detection of circulating tumor DNA from non‐small cell lung cancer brain metastasis in cerebrospinal fluid samples

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