Serial genome-wide sequencing of cell-free DNA (cfDNA) by assays used in non-invasive prenatal testing (NIPT) to identify copy number alterations (CNAs) associated with immunotherapy response.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e14533-e14533
Author(s):  
Aaron Goodman ◽  
Taylor Jensen ◽  
Shumei Kato ◽  
Christopher Ellison ◽  
Lisa Tran ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Peripheral Blood ◽  
Prenatal Testing ◽  
Quantitative Detection ◽  
Initial Increase ◽  
Continuous Increase ◽  
Genome Wide ◽  
A Genome ◽  
The Mean ◽  
Sustained Increase

e14533 Background: cfDNA derived from tumor cells can be detected in the plasma of many cancer patients. Noninvasive methods to detect CNAs have been developed to detect chromosomal abnormalities in the setting of prenatal screening. We hypothesized that similar methods can be used to enable quantitative detection of CNAs in cfDNA, as represented by a genome instability number (GIN), in patients with cancer and used to monitor response to immunotherapy. Methods: Peripheral blood for CNA analysis was collected from patients with diverse cancers for whom immunotherapy was planned. Plasma was separated from peripheral blood using centrifugation. cfDNA was collected and subjected to low-coverage, genome-wide sequencing. CNAs were detected using methods developed for noninvasive prenatal testing. GIN was calculated as the cumulative sum of the deviation from baseline for all detected autosomal CNAs. The current analysis focused on patients with a complete or partial response (CR/PR) or progressive disease (PD). Results: Of 48 patients, 11 (23%) attained CR/PR; 17 (35%), PD; 20, stable disease. Twelve of the 28 patients (43%) with CR/PR (5 (42%)) or PD (7 (58%)) had a GIN value consistent with the presence of CNAs at treatment initiation and ≥ 1 additional sample for comparison. Four of the 5 patients with CR/PR had a decrease in their GIN from their baseline while all 7 patients with PD had a sustained increase in their GIN. The mean (standard error of the mean (SEM)) change in GIN from maximum to minimum for responders was –2753.8 (+/-1643); mean (SEM) change in GIN from minimum to maximum for progressors was 1373.76 (+/-576) (p = 0.0221). Interestingly, 3 of the 5 responders had an initial increase in their GIN after 2-3 weeks of treatment followed by a decline, while all 7 progressors had a continuous increase in their GIN. Conclusions: GIN can be used to monitor response to immune checkpoint inhibitors in cancer patients. Serial evaluation shows an initial GIN increase followed by decline in patients who eventually attain CR/PR, but a sustained increase in patients with progression.

Clinical Relevance of Plasma DNA Methylation in Colorectal Cancer Patients Identified by Using a Genome-Wide High-Resolution Array

2014 ◽  
Vol 22 (S3) ◽  
pp. 1419-1427 ◽  
Author(s):  
Pei-Ching Lin ◽  
Jen-Kou Lin ◽  
Chien-Hsing Lin ◽  
Hung-Hsin Lin ◽  
Shung-Haur Yang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Dna Methylation ◽  
High Resolution ◽  
Cancer Patients ◽  
Clinical Relevance ◽  
Plasma Dna ◽  
Genome Wide ◽  
A Genome ◽  
Colorectal Cancer Patients

scholarly journals Allelotyping of Follicular Thyroid Carcinoma: Frequent Allelic Losses in Chromosome Arms 7q, 11p, and 22q

2001 ◽  
Vol 86 (9) ◽  
pp. 4268-4272 ◽  
Author(s):  
Yutaka Kitamura ◽  
Kazuo Shimizu ◽  
Koichi Ito ◽  
Shigeo Tanaka ◽  
Mitsuru Emi
Keyword(s):  
Thyroid Carcinoma ◽  
Follicular Thyroid Carcinoma ◽  
Allelic Loss ◽  
Mean Frequency ◽  
Thyroid Carcinomas ◽  
Real Frequency ◽  
Genome Wide ◽  
A Genome ◽  
Genetic Mechanisms ◽  
The Mean

The genetic mechanisms involved in development of follicular thyroid carcinoma are poorly understood, although allelic losses (LOH) in this type of tumor have been reported in small panels of follicular thyroid carcinomas examined in earlier studies. To clarify the real frequency of allelic loss we carried out a genome-wide allelotyping study of 66 follicular thyroid carcinomas using 39 microsatellite markers representing all nonacrocentric autosomal arms. The mean frequency of LOH was 9.2%, and the mean fractional allelic loss was 0.09. The most frequent allelic losses were detected in 7q (28%), 11p (28%), and 22q (41%). When we compared these results with our previous allelotyping studies using identical markers in other types of thyroid cancers, the 9.2% mean frequency of allelic loss detected in follicular thyroid carcinomas was higher than that in papillary thyroid carcinomas (3%), but not as high as that detected in anaplastic thyroid carcinomas (20%). Frequent allelic losses of markers on chromosomes 7q, 11p, and 22q suggest locations to examine for the presence of suppressor genes associated with the development of follicular thyroid carcinoma.

A genome-wide association study identifies four genetic markers for hematological toxicities in cancer patients receiving gemcitabine therapy

2012 ◽  
Vol 22 (4) ◽  
pp. 229-235 ◽  
Author(s):  
Kazuma Kiyotani ◽  
Satoko Uno ◽  
Taisei Mushiroda ◽  
Atsushi Takahashi ◽  
Michiaki Kubo ◽  
...  
Keyword(s):  
Association Study ◽  
Cancer Patients ◽  
Genetic Markers ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Genome Wide ◽  
A Genome

scholarly journals Breast Cancer Detection and Treatment Monitoring Using a Noninvasive Prenatal Testing Platform: Utility in Pregnant and Nonpregnant Populations

2020 ◽  
Vol 66 (11) ◽  
pp. 1414-1423
Author(s):  
Liesbeth Lenaerts ◽  
Huiwen Che ◽  
Nathalie Brison ◽  
Maria Neofytou ◽  
Tatjana Jatsenko ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Treatment Response ◽  
Cancer Detection ◽  
Prenatal Testing ◽  
Treatment Monitoring ◽  
Breast Cancer Detection ◽  
Maternal Circulation ◽  
Noninvasive Prenatal Testing ◽  
Genome Wide ◽  
A Genome

Abstract Background Numerous publications have reported the incidental detection of occult malignancies upon routine noninvasive prenatal testing (NIPT). However, these studies were not designed to evaluate the NIPT performance for cancer detection. Methods We investigated the sensitivity of a genome-wide NIPT pipeline, called GIPSeq, for detecting cancer-specific copy number alterations (CNAs) in plasma tumor DNA (ctDNA) of patients with breast cancer. To assess whether a pregnancy itself, with fetal cell-free DNA (cfDNA) in the maternal circulation, might influence the detection of ctDNA, results were compared in pregnant (n = 25) and nonpregnant (n = 25) cancer patients. Furthermore, the ability of GIPSeq to monitor treatment response was assessed. Results Overall GIPSeq sensitivity for detecting cancer-specific CNAs in plasma cfDNA was 26%. Fifteen percent of detected cases were asymptomatic at the time of blood sampling. GIPSeq sensitivity mainly depended on the tumor stage. Also, triple negative breast cancers (TNBC) were more frequently identified compared to hormone-positive or HER2-enriched tumors. This might be due to the presence of high-level gains and losses of cfDNA or high ctDNA loads in plasma of TNBC. Although higher GIPSeq sensitivity was noted in pregnant (36%) than in nonpregnant women (16%), the limited sample size prohibits a definite conclusion. Finally, GIPSeq profiling of cfDNA during therapy allowed monitoring of early treatment response. Conclusions The results underscore the potential of NIPT-based tests, analyzing CNAs in plasma cfDNA in a genome-wide and unbiased fashion for breast cancer detection, cancer subtyping and treatment monitoring in a pregnant and nonpregnant target population.

scholarly journals PRICKLE1 × FOCAD Interaction Revealed by Genome-Wide vQTL Analysis of Human Facial Traits

2021 ◽  
Vol 12 ◽  
Author(s):  
Dongjing Liu ◽  
Hyo-Jeong Ban ◽  
Ahmed M. El Sergani ◽  
Myoung Keun Lee ◽  
Jacqueline T. Hecht ◽  
...  
Keyword(s):  
Phenotypic Variability ◽  
Strong Support ◽  
Variable Structure ◽  
Cranial Base ◽  
Facial Morphology ◽  
Genome Wide ◽  
A Genome ◽  
Trait Variance ◽  
Mean Size ◽  
The Mean

The human face is a highly complex and variable structure resulting from the intricate coordination of numerous genetic and non-genetic factors. Hundreds of genomic loci impacting quantitative facial features have been identified. While these associations have been shown to influence morphology by altering the mean size and shape of facial measures, their effect on trait variance remains unclear. We conducted a genome-wide association analysis for the variance of 20 quantitative facial measurements in 2,447 European individuals and identified several suggestive variance quantitative trait loci (vQTLs). These vQTLs guided us to conduct an efficient search for gene-by-gene (G × G) interactions, which uncovered an interaction between PRICKLE1 and FOCAD affecting cranial base width. We replicated this G × G interaction signal at the locus level in an additional 5,128 Korean individuals. We used the hypomorphic Prickle1Beetlejuice (Prickle1Bj) mouse line to directly test the function of Prickle1 on the cranial base and observed wider cranial bases in Prickle1Bj/Bj. Importantly, we observed that the Prickle1 and Focadhesin proteins co-localize in murine cranial base chondrocytes, and this co-localization is abnormal in the Prickle1Bj/Bj mutants. Taken together, our findings uncovered a novel G × G interaction effect in humans with strong support from both epidemiological and molecular studies. These results highlight the potential of studying measures of phenotypic variability in gene mapping studies of facial morphology.

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