The mutational landscape of circulating cell-free DNA to identify neoadjuvant chemotherapy response in colorectal cancer patients.

e15096 Background: The neoadjuvant chemotherapy plays an important role in the current treatment of colorectal cancer (CRC), even though parts of patients could not be benefit from it. This study was aimed to explore the specific mutational profile of plasma cell free DNA (cfDNA) in CRC patients with or without response to neoadjuvant chemotherapy. Methods: 16 eligible CRC patients were enrolled in this study from Harbin Medical University Cancer Hospital. These patients were divided into two groups: with response ( R, n = 8) and without response (NR, n = 8) to neoadjuvant chemotherapy. All patients received neoadjuvant chemotherapy and their baseline blood samples were collected. The cfDNA fragments were extracted for enrichment of a panel covering exon regions of 1,086 genes. Gene alterations were analyzed to investigate the relationship between genetic characterizations of cfDNA and response to neoadjuvant chemotherapy. Results: Principal component (PCA) analysis for copy number variation(CNV) of cfDNA differed significantly in two groups. In the R group, there were higher frequency CNV loss in ABL-1, ERBB3, SMO, IGF1R, AURKA, PDGFRA, IDH1, BRAF, PIK3CB, NRAS, NF1, MITF, PTCH1 genes, and CNV gain in MTRR, HSP90AA1, VHL, CREBBP, CHEK2, DDR2, MUTYH, NCOA1, XPC, FANCA genes. Regarding to the area under the ROC curve, CNV of these genes had a high value of 0.967, which implied that CNV of the candidate genes have predictive value for identifying response to neoadjuvant chemotherapy in CRC patients. Furthermore, the Copy Number Instability (CNI) value of R group was significantly higher than NR group(p = 0.0014). Conclusions: The candidate genes’ copy number variation and CNI value of baseline plasma cfDNA can identify the colorectal cancer patients with response or without response to neoadjuvant chemotherapy in this small cohort. The molecular profile of cfDNA in plasma may be a potential biomarker for predicting the response to neoadjuvant chemotherapy in colorectal cancer patients. These findings warrant further expanded prospective cohorts to validate.

Download Full-text

Genome-Wide Copy Number Variation of Circulating Cell-Free DNA As a Biomarker in Head and Neck Cancer Patients Treated With Immunotherapy

SSRN Electronic Journal ◽

10.2139/ssrn.3965384 ◽

2021 ◽

Author(s):

Yunshu Zhu ◽

Sheng Yang ◽

Liping Jiang ◽

Xiaobing Wang ◽

Xiaohui He

Keyword(s):

Head And Neck Cancer ◽

Copy Number Variation ◽

Head And Neck ◽

Cancer Patients ◽

Neck Cancer ◽

Copy Number ◽

Cell Free Dna ◽

Free Dna ◽

Genome Wide ◽

Number Variation

Download Full-text

26P Genome-wide copy number variation of circulating cell-free DNA as a biomarker in head and neck cancer patients treated with immunotherapy

Annals of Oncology ◽

10.1016/j.annonc.2021.10.042 ◽

2021 ◽

Vol 32 ◽

pp. S1384

Author(s):

Y. Zhu ◽

S. Yang ◽

L. Jiang ◽

X. Wang ◽

X. He

Keyword(s):

Head And Neck Cancer ◽

Copy Number Variation ◽

Head And Neck ◽

Cancer Patients ◽

Neck Cancer ◽

Copy Number ◽

Cell Free Dna ◽

Free Dna ◽

Genome Wide ◽

Number Variation

Download Full-text

Association of mitochondrial copy number variation and T16189C polymorphism with colorectal cancer in North Indian population

Tumor Biology ◽

10.1177/1010428317740296 ◽

2017 ◽

Vol 39 (11) ◽

pp. 101042831774029 ◽

Cited By ~ 11

Author(s):

Bhupender Kumar ◽

Zafar Iqbal Bhat ◽

Savita Bansal ◽

Sunil Saini ◽

Afreen Naseem ◽

...

Keyword(s):

Colorectal Cancer ◽

Copy Number Variation ◽

Odds Ratio ◽

Copy Number ◽

Indian Population ◽

Chain Reaction ◽

Mitochondrial Copy Number ◽

Number Variation ◽

Polymerase Chain ◽

Colorectal Cancer Patients

Globally, colorectal cancer is the third most common type of cancer. Genetic instability leading to cancer development is one of the major causes for development of cancer. Alterations in mitochondrial genome, that is, mutations, single-nucleotide polymorphisms, and copy number variations are known to contribute in cancer development. The aim of our study was to investigate association of mitochondrial T16189C polymorphism and copy number variation with colorectal cancer in North Indian population. DNA isolated from peripheral blood of 126 colorectal cancer patients and 114 healthy North Indian subjects was analyzed for T16189C polymorphism and half of them for mitochondrial copy number variation. Genotyping was done using polymerase chain reaction–restriction fragment length polymorphism, and copy number variation was estimated using real-time polymerase chain reaction, numbers of mitochondrial copies and found to be significantly higher in colorectal cancer patients than healthy controls (88 (58–154), p = 0.001). In the regression analysis, increased mitochondrial copy number variation was associated with risk of colorectal cancer (odds ratio = 2.885, 95% confidence interval = 1.3–6.358). However, T16189C polymorphism was found to be significantly associated with the risk of rectal cancer (odds ratio = 5.213, p = 0.001) and non-significantly with colon cancer (odds ratio = 0.867, p = 0.791). Also, false-positive report probability analysis was done to validate the significant findings. Our results here indicate that mitochondrial copy number variation may be playing an important role in the development of colorectal cancer, and detection of mitochondrial copy number variation can be used as a biomarker for predicting the risk of colorectal cancer in North Indian subjects.

Download Full-text