Monitoring of circulating tumour-associated DNA as a prognostic tool for oral squamous cell carcinoma

Hamana, Katsumi; Uzawa, Katsuhiro; Ogawara, Katsunori; Shiiba, Masashi; Bukawa, Hiroki; Yokoe, Hidetaka; Tanzawa, Hideki

doi:10.1038/sj.bjc.6602635

Cited by 53 publications

(34 citation statements)

References 14 publications

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“…Only 19% of LOH in the highand 27% in the low-molecular weight plasma DNA were concordant before and after therapy, indicating considerable therapy-induced changes in LOH patterns. To date, several clinical studies have described microsatellite alterations in follow-up sera of patients with different cancer entities (42,43). A similar observation has also been described in patients with small cell lung cancer (SCLC) patients.…”

Section: Discussionmentioning

confidence: 72%

Loss of Heterozygosity at Tumor Suppressor Genes Detectable on Fractionated Circulating Cell-Free Tumor DNA as Indicator of Breast Cancer Progression

Schwarzenbach

Eichelser

Kropidlowski

et al. 2012

Clinical Cancer Research

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Purpose: LOH on circulating DNA may provide tumor-specific information on breast cancer. As identification of LOH on cell-free DNA is impeded by the prevalence of wild type DNA in blood of cancer patients, we fractionated plasma DNA, and determined the diagnostic and prognostic value of both fractions.Experimental design: Our cohort of 388 patients with primary breast cancer before chemotherapy was selected from a multicenter study (SUCCESS). Postoperative plasma was fractionated in low-and highmolecular weight DNA by two different column systems. In both fractions, LOH was determined by a PCRbased microsatellite analysis using a panel of 8 polymorphic markers. Circulating tumor DNA in plasma from 30 patients after chemotherapy was additionally analyzed. The significance levels were adjusted for multiple comparisons.Results: More patients (38%) had LOH at all markers in the fraction containing short DNA fragments than in the fraction containing the long DNA molecules (28%, P ¼ 0.0001). In both fractions 32.85% of LOH were concordant. LOH at the markers D3S1605, D10S1765, D12S1725, D13S218, and D17S855 significantly correlated with tumor stage, tumor size, and lymph node metastasis, positive progesterone, and HER2 receptor status. Most importantly, LOH at D12S1725 mapping to cyclin D2 correlated with shorter overall survival (P ¼ 0.004).Conclusions: The improved detection of LOH on cell-free DNA provides important information on DNA losses of tumor suppressor genes TIG1, PTEN, cyclin D2, RB1, and BRCA1 in breast cancer. In particular, loss of the cyclin D2 gene might become an important prognostic marker easily detectable in the peripheral blood. Clin Cancer Res; 18(20); 5719-30. Ó2012 AACR.

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Section: Discussionmentioning

confidence: 72%

Loss of Heterozygosity at Tumor Suppressor Genes Detectable on Fractionated Circulating Cell-Free Tumor DNA as Indicator of Breast Cancer Progression

Schwarzenbach

Eichelser

Kropidlowski

et al. 2012

Clinical Cancer Research

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“…In >50% of patients, allelic imbalances were identified in serum DNA that corresponded with tumor DNA. In turn, a correlation was found between allelic imbalances in serum DNA and tumor stage [32] . Although the use of microsatellites has been a subject of debate [36] , these results are promising.…”

Section: Liquid Biopsymentioning

confidence: 91%

“…Additionally, in patients with a malignant tumor, blood can contain CTCs and ctDNA [25][26][27] , probably released into the bloodstream by the (metastatic) tumor cells following apoptosis and necrosis, or by the active release of living cells [28] . cfDNA has already been studied clinically in prenatal testing, and transplant and trauma patients [29,30] , while ctDNA is considered to be a potential prognostic tool in cancer treatment [31,32] .…”

Section: Liquid Biopsymentioning

confidence: 99%

Liquid Biopsy: A Future Tool for Posttreatment Surveillance in Head and Neck Cancer?

Ginkel

Huibers²,

Noorlag

et al. 2016

Pathobiology

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The prognosis of head and neck squamous cell carcinoma (HNSCC) is largely based on disease stage. Despite improvements in treatment, recurrence rates are still considered high. Currently, disease progression or regression after curative treatment is monitored by clinical evaluation combined with flexible endoscopy and/or imaging. However, specificity of imaging is low due to the posttreatment effects. Detection of circulating tumor DNA (ctDNA) from blood samples of HNSCC patients is a minimally invasive technique that could lead to an earlier detection of recurrence. In addition, digital droplet PCR (ddPCR) could be used to sensitively detect these mutational targets. Future study on ctDNA using ddPCR in blood samples of HNSCC patients is recommended during the follow-up stage to detect recurrences in a timely manner.

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“…We note the recent paper of Hamana et al (2005) in your journal with interest and have some observations in the light of a similar pilot study that we presented last year at the 2004 International Conference on Head & Neck Cancer (Thomas et al, 2004).…”

Section: Sirmentioning

confidence: 99%

Monitoring of circulating tumour-associated DNA as a prognostic tool for oral squamous cell carcinoma

2005

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). Our study aimed to establish whether genetic alterations observed in preoperative circulating DNA were maintained after surgical treatment and if this could be related to outcome. Similarly to the Hamana study, DNA was isolated from tumour tissue, white blood cells as control DNA, pre-and postoperative plasma from each of six oral cancer patients and microsatellite analysis was used to measure allelic imbalance (AI). However, in our study 22 markers were used instead of nine, with the result that AI was detected in 100% of tumours (six of six) rather than the 59% (38 of 64) observed in the Hamana study. Our markers were also chosen to include those that have previously demonstrated AI in oral SCC and we were surprised to note that Hamana et al did not include any markers from 3p21, 3p14 or 17p13.1. The other main difference in our study was that our clinical follow-up and investigation of plasma specimens continued for a minimum of 2 years.In four of six (67%) of our patients, presurgery circulating DNA showed allelic imbalance at 41 locus that demonstrated AI in tumour DNA. This is similar to the data obtained by Hamana et al, who observed AI in preoperative plasma in 28 of their 38 (74%) patients with AI-positive tumours. Although we have no data immediately postsurgery, it was interesting to note that the incidence of AI in circulating DNA in the Hamana study DECREASED (13 of 38; 34%) at this time point, when it would be expected to remain high due to tumour-specific DNA persisting in the circulation before degradation and clearance. However, the authors do not indicate the exact time of sampling for their postsurgery plasma and these data may be a result of reduced sensitivity of the AI technique when nontumour DNA is released into the bloodstream during the trauma of surgery. Our postoperative follow-up plasma samples were obtained at 24 -48 months and AI was retained at five of the nine and one of the eight markers in samples from two patients who developed locoregional recurrence. None of our patients developed distant metastases. Our data show the potential for this technique in the early detection of locoregional recurrence and augments the data of Hamana et al, which shows value in predicting distant metastases. Indeed their data suggest that persistence of DNA aberrations at 4 weeks after surgery had a 100% positive predictive value for distant metastases. Four weeks is often the point used to prescribe postoperative radiotherapy or combined chemo-radiotherapy (POCRT). In the context of recent trials advocating POCRT in poor prognosis head and neck cancer (Cooper et al, 2004;Bernier et al, 2005), this finding offers promise in clinical translation.The potential for use of circulating DNA in head and neck cancer has been demonstrated by this and other studies (NawrozDanish et al, 2004); however, the question arises as to the best method of analysing genetic or epigenetic aberrations. Most patients are noninformative for at least one marker and these AI techniques become insensitive in the face of 'c...

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Monitoring of circulating tumour-associated DNA as a prognostic tool for oral squamous cell carcinoma

Cited by 53 publications

References 14 publications

Loss of Heterozygosity at Tumor Suppressor Genes Detectable on Fractionated Circulating Cell-Free Tumor DNA as Indicator of Breast Cancer Progression

Loss of Heterozygosity at Tumor Suppressor Genes Detectable on Fractionated Circulating Cell-Free Tumor DNA as Indicator of Breast Cancer Progression

Liquid Biopsy: A Future Tool for Posttreatment Surveillance in Head and Neck Cancer?

Monitoring of circulating tumour-associated DNA as a prognostic tool for oral squamous cell carcinoma

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