Short interspersed CAN SINE elements as prognostic markers in canine mammary neoplasia

Gelaleti, Gabriela Bottaro; Granzotto, Adriana; Leonel, Camila; Jardim, Bruna Victorasso; Moschetta, Marina Gobbe; Carareto, Claudia M. A.; Zuccari, Débora A.P.C.

doi:10.3892/or.2013.2827

Cited by 6 publications

(12 citation statements)

References 45 publications

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“…Individual variability of cfDNA values was generally very high, as previously reported both in dogs [16,18] and humans [48–50], particularly in necrotic tumors.…”

Section: Discussionsupporting

confidence: 72%

“…To date, circulating cfDNA in blood has been considered a promising biomarker in some human tumors and, today, cfDNA fragmentation represented by the integrity index (ratio between long and short cfDNA fragments) is studied for its ability to discriminate cancer patients from healthy controls [29]. Very few data are available for the canine species [16–18]. …”

Section: Discussionmentioning

confidence: 99%

“…Conversely, one study targeted SINE sequences into the bloodstream of 28 neoplastic subjects and detected a prognostic significance [18]. Further prospective analysis with robust follow-up data should be prompted to better elucidate this aspect.…”

Section: Discussionmentioning

confidence: 99%

“…In recent years, measuring circulating cell-free DNA (cfDNA) in plasma has gained attention as a biomarker in some human tumors, such as pancreatic cancer [11], breast tumors [12,13], and rectal cancer [14,15]. Little, but promising, information is present in veterinary medicine [16–18]. Several hypotheses have been postulated about cfDNA origin: its presence in the bloodstream could be due to i) DNA leakage resulting from tumor necrosis or apoptosis, ii) lysis of circulating cancer cells or micrometastases, or iii) unrevealed mechanism of active and spontaneous release [19,20].…”

Section: Introductionmentioning

confidence: 99%

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Circulating Cell-Free DNA in Dogs with Mammary Tumors: Short and Long Fragments and Integrity Index

et al. 2017

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Circulating cell-free DNA (cfDNA) has been considered an interesting diagnostic/prognostic plasma biomarker in tumor-bearing subjects. In cancer patients, cfDNA can hypothetically derive from tumor necrosis/apoptosis, lysed circulating cells, and some yet unrevealed mechanisms of active release. This study aimed to preliminarily analyze cfDNA in dogs with canine mammary tumors (CMTs). Forty-four neoplastic, 17 non-neoplastic disease-bearing, and 15 healthy dogs were recruited. Necrosis and apoptosis were also assessed as potential source of cfDNA on 78 CMTs diagnosed from the 44 dogs. The cfDNA fragments and integrity index significantly differentiated neoplastic versus non-neoplastic dogs (P<0.05), and allowed the distinction between benign and malignant lesions (P<0.05). Even if without statistical significance, the amount of cfDNA was also affected by tumor necrosis and correlated with tumor size and apoptotic markers expression. A significant (P<0.01) increase of Bcl-2 in malignant tumors was observed, and in metastatic CMTs the evasion of apoptosis was also suggested. This study, therefore, provides evidence that cfDNA could be a diagnostic marker in dogs carrying mammary nodules suggesting that its potential application in early diagnostic procedures should be further investigated.

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“…Individual variability of cfDNA values was generally very high, as previously reported both in dogs [16,18] and humans [48–50], particularly in necrotic tumors.…”

Section: Discussionsupporting

confidence: 72%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Circulating Cell-Free DNA in Dogs with Mammary Tumors: Short and Long Fragments and Integrity Index

et al. 2017

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“…On the other hand, instead of studying individual genes and their epigenetic aberrations, there have also been attempts to search for a candidate biomarker using cfDNA and repetitive elements, such as short interspersed nuclear element (SINE, represented by ALU) 26 . SINEs that are small and non-autonomous transposable element has been suggested as prognostic markers of canine mammary tumor without association of DNA methylation 27,28 , whereas there have been no previous attempts to use LINE-1s and its methylation as a biomarker for the liquid biopsy of breast cancer.…”

Section: Discussionmentioning

confidence: 99%

Methylation of LINE-1 in cell-free DNA serves as a liquid biopsy biomarker for human breast cancers and dog mammary tumors

Lee

Shin

Kim

et al. 2019

Sci Rep

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Breast cancer (BC) is one of the most common cancers in both women and female dogs. Methylation changes of LINE-1 have been reported in human cancers. The aim of this study was to determine the hypomethylation of canine LINE-1 in liquid biopsies for canine mammary tumors (CMT) and to assess its diagnostic performance in human plasma. BC associated LINE-1 methylation was measured by methylation sensitive (HpaII) and insensitive (MspI) restriction enzyme digestion followed by real-time PCR using the cfDNA isolated from 300 µl of plasma. The relative level of methylated canine LINE-1 was less than 0.4 in the benign and malignant CMTs (0.29 ± 0.061 and 0.39 ± 0.066, respectively) when it was 0.92 ± 0.067 in the healthy controls. The area under the ROC curve (AUC) was significantly high in both benign and malignant tumors (0.97 and 0.93). Furthermore, this approach was also successfully implemented in a set of 26 human BCs with 10 healthy controls (AUC = 0.78). Altogether, our data suggest that the comparative approach using a dog model might be helpful to rapidly develop a new diagnostic biomarker and that the methylation of LINE-1 in cfDNA may be a good target as a diagnostic marker of both human BC and CMT.

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Impact of preanalytical factors on liquid biopsy in the canine cancer model

Megquier,

Husted,

Rhoades

et al. 2024

Preprint

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While liquid biopsy has potential to transform cancer diagnostics through minimally-invasive detection and monitoring of tumors, the impact of preanalytical factors such as the timing and anatomical location of blood draw is not well understood. To address this gap, we leveraged pet dogs with spontaneous cancer as a model system, as their compressed disease timeline facilitates rapid diagnostic benchmarking. Key liquid biopsy metrics from dogs were consistent with existing reports from human patients. The tumor content of samples was higher from venipuncture sites closer to the tumor and from a central vein. Metrics also differed between lymphoma and non-hematopoietic cancers, urging cancer-type-specific interpretation. Liquid biopsy was highly sensitive to disease status, with changes identified soon after post chemotherapy administration, and trends of increased tumor fraction and other metrics observed prior to clinical relapse in dogs with lymphoma or osteosarcoma. These data support the utility of pet dogs with cancer as a relevant system for advancing liquid biopsy platforms.

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Short interspersed CAN SINE elements as prognostic markers in canine mammary neoplasia

Cited by 6 publications

References 45 publications

Circulating Cell-Free DNA in Dogs with Mammary Tumors: Short and Long Fragments and Integrity Index

Circulating Cell-Free DNA in Dogs with Mammary Tumors: Short and Long Fragments and Integrity Index

Methylation of LINE-1 in cell-free DNA serves as a liquid biopsy biomarker for human breast cancers and dog mammary tumors

Impact of preanalytical factors on liquid biopsy in the canine cancer model

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