Somatic Alterations and Implications in Breast Cancer

2009 ◽  
pp. 183-213 ◽  
Author(s):  
Carl Ton ◽  
Jamie Guenthoer ◽  
Peggy L. Porter
Keyword(s):  
Breast Cancer ◽  
Somatic Alterations

scholarly journals Pan-Cancer Analysis Reveals the Signature of TMC Family of Genes as a Promising Biomarker for Prognosis and Immunotherapeutic Response

2021 ◽  
Vol 12 ◽  
Author(s):  
Jing Song ◽  
Yongyao Tang ◽  
Xiaoyong Luo ◽  
Xinpeng Shi ◽  
Fangzhou Song ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune Cell ◽  
Human Cancer ◽  
Critical Role ◽  
Survival Rates ◽  
Response Prediction ◽  
Skin Melanoma ◽  
Transmembrane Channel ◽  
Mutation Burden ◽  
Somatic Alterations

Transmembrane Channel-like (TMC) genes are critical in the carcinogenesis, proliferation, and cell cycle of human cancers. However, the multi-omics features of TMCs and their role in the prognosis and immunotherapeutic response of human cancer have not been explored. We discovered that TMCs 4-8 were commonly deregulated and correlated with patient survival in a variety of cancers. For example, TMC5 and TMC8 were correlated with the relapse and overall survival rates of breast cancer and skin melanoma, respectively. These results were validated by multiple independent cohorts. TMCs were regulated by DNA methylation and somatic alterations, such as TMC5 amplification in breast cancer (523/1062, 49.2%). Six algorithms concordantly uncovered the critical role of TMCs in the tumor microenvironment, potentially regulating immune cell toxicity and lymphocytes infiltration. Moreover, TMCs 4-8 were correlated with tumor mutation burden and expression of PD-1/PD-L1/CTLA4 in 33 cancers. Thus, we established an immunotherapy response prediction (IRP) score based on the signature of TMCs 4-8. Patients with higher IRP scores showed higher immunotherapeutic responses in five cohorts of skin melanoma (area under curve [AUC] = 0.90 in the training cohort, AUCs range from 0.70 to 0.83 in the validation cohorts). Together, our study highlights the great potential of TMCs as biomarkers for prognosis and immunotherapeutic response, which can pave the way for further investigation of the tumor-infiltrating mechanisms and therapeutic potentials of TMCs in cancer.

scholarly journals Short somatic alterations at the site of copy number variation in breast cancer

2020 ◽  
Vol 112 (1) ◽  
pp. 444-453
Author(s):  
Fumi Murakami ◽  
Yumi Tsuboi ◽  
Yuka Takahashi ◽  
Yoshiya Horimoto ◽  
Kaoru Mogushi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Copy Number Variation ◽  
Copy Number ◽  
Number Variation ◽  
Somatic Alterations

scholarly journals Characterisation of PALB2 tumours through whole-exome and whole-transcriptomic analyses

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Pei Sze Ng ◽  
Jia Wern Pan ◽  
Muhammad Mamduh Ahmad Zabidi ◽  
Pathmanathan Rajadurai ◽  
Cheng Har Yip ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Homologous Recombination ◽  
Peripheral Blood Lymphocytes ◽  
Molecular Characteristics ◽  
Breast Cancer Patients ◽  
Mutational Status ◽  
Whole Exome ◽  
Increased Risk ◽  
Fresh Frozen ◽  
Somatic Alterations

AbstractRare protein-truncating variants (PTVs) in PALB2 confer increased risk to breast cancer, but relatively few studies have reported the characteristics of tumours with PALB2 PTVs. In this study, we describe molecular characteristics of tumours with either germline or somatic alterations in PALB2. DNA from fresh frozen tumour tissues and matched peripheral blood lymphocytes for 560 breast cancer patients was subjected for whole-exome sequencing (WES), and RNA from tumour tissues was subjected to RNA sequencing (RNA-seq). We found six cases with germline and three with somatic protein-truncating variants in PALB2. The characteristics of tumours in patients with PALB2 PTVs were similar to those with BRCA1 and BRCA2 PTVs, having significantly more somatic alterations, and a high proportion of the mutational signature and genomic scar scores characteristic of deficiencies in homologous recombination (HR), compared to tumours arising in non-carriers. Unlike tumours arising in patients with BRCA1 and BRCA2 PTVs, PALB2 tumours did not have high prevalence of TP53 somatic alterations or an enriched immune microenvironment. In summary, PALB2 tumours show the homologous recombination deficiencies characteristic of BRCA1 and BRCA2 tumours, and highlight the potential clinical relevance of PALB2 mutational status in guiding therapeutic choices.

Identification of pathogenic ROS1 alterations in cell-free DNA (cfDNA) from patients with breast cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 1031-1031
Author(s):  
Jeremy Meyer Force ◽  
Mary Love Taylor ◽  
Leylah Drusbosky ◽  
Jennifer Yen ◽  
Paul Kelly Marcom ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Amino Acid ◽  
Tyrosine Kinase Receptor ◽  
Cancer Tissue ◽  
Fusion Partner ◽  
Single Nucleotide Variants ◽  
Genomic Alterations ◽  
Conserved Regions ◽  
Somatic Alterations

1031 Background: ROS1 is an important proto-oncogene involved in the development of various cancers for which we have FDA approved therapies. While activation of the ROS1 tyrosine kinase receptor has been reported in 1-2% of lung cancers, the frequency and type of ROS1 alterations in breast cancer have not been fully explored. We previously described the incidence of ROS1 alterations from breast cancer tissue. The purpose of this study was to identify the incidence of ROS1 genomic alterations occurring in cfDNA from patients with breast cancer. Methods: We queried 16,053 breast cancer samples from the Guardant Health breast cancer database between June 2015 - October 2019 to identify the incidence of ROS1 alterations detected in cfDNA in breast cancer. We identified fusion partner genes and classified each alteration type into the following categories: fusion, single nucleotide variants (SNVs), and indels. Radical amino acid changes occurring at conserved regions across the ROS1 gene were identified. In vitro analyses were used to investigate the effect of ROS1 nonsynonymous mutations on the ROS1 protein. We made associations with ROS1 alterations and co-occurring mutated genes. Results: Nonsynonymous ROS1 alterations from the Guardant Health breast cancer database were found in 162 samples from 142 patients in the 16,053-patient cohort (1%). Alterations found included: 1 (0.6%) ROS1-SLC35F1 fusion, 155 (95.7%) SNVs, and 6 (3.7%) indels. Of the 155 SNVs, we identified 23 (14.8%) mutations occurring in the ROS1 kinase, of which, 20 (12.9%) occurred at highly conserved regions and 15 (9.6%) harbored radical amino acid changes. The top 5 co-occurring mutations in samples with ROS1 alterations were TP53 (50%), PIK3CA (44%), ESR1 (27%), EGFR (21%), and FGFR1 (18%). Conclusions: A modest incidence of ROS1 genomic alterations occurs in cfDNA from patients with breast cancer. New somatic alterations in the ROS1 gene were identified from Guardant Health that were not detected in publicly available databases. A portion of mutations occurred at highly conserved regions across the ROS1 gene suggesting these may be more actionable than currently recognized. In vitro analyses of ROS1 gene activation from these newly discovered somatic alterations are being investigated with results to be reported. Co-occurring mutations reveal a unique genotype associated with ROS1 alterations that may play a biologic role in ROS1-mediated pathogenesis.

scholarly journals A Pilot Study for the Feasibility of Exome-Sequencing in Circulating Tumor Cells Versus Single Metastatic Biopsies in Breast Cancer

2020 ◽  
Vol 21 (14) ◽  
pp. 4826
Author(s):  
Pushpinder Kaur ◽  
Daniel Campo ◽  
Tania B. Porras ◽  
Alexander Ring ◽  
Janice Lu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Exome Sequencing ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Copy Number ◽  
Chromosomal Rearrangements ◽  
Gene Mutations ◽  
Clinical Samples ◽  
Breast Cancer Patients ◽  
Somatic Alterations

The comparison of the landscape of somatic alterations in circulating tumor cells (CTCs) versus metastases is challenging. Here, we comprehensively characterized the somatic landscape in bulk (amplified and non-amplified), spike-in breast cancer cells, CTCs, and metastases from breast cancer patients using whole-exome sequencing (WES). We determined the level of genomic concordance for somatic nucleotide variants (SNVs), copy number alterations (CNAs), and structural variants (SVs). The variant allele fractions (VAFs) of somatic variants were remarkably similar between amplified and non-amplified cell line samples as technical replicates. In clinical samples, a significant fraction of somatic variants had low VAFs in CTCs compared to metastases. The most frequently recurrent gene mutations in clinical samples were associated with an elevated C > T mutational signature. We found complex rearrangement patterns including intra- and inter-chromosomal rearrangements, singleton, and recurrent gene fusions, and tandem duplications. We observed high molecular discordance for somatic alterations between paired samples consistent with marked heterogeneity of the somatic landscape. The most prevalent copy number calls were focal deletion events in CTCs and metastases. Our results demonstrate the feasibility of an integrated workflow for the identification of a complete repertoire of somatic alterations and highlight the intrapatient genomic differences that occur between CTCs and metastases.

scholarly journals Novel insights into breast cancer copy number genetic heterogeneity revealed by single-cell genome sequencing

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Timour Baslan ◽  
Jude Kendall ◽  
Konstantin Volyanskyy ◽  
Katherine McNamara ◽  
Hilary Cox ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Single Cell ◽  
Genetic Heterogeneity ◽  
Copy Number ◽  
Breast Cancers ◽  
Genomic Location ◽  
Cancer Genomes ◽  
Somatic Alterations ◽  
Cell Genome ◽  
Chromosomal Amplifications

Copy number alterations (CNAs) play an important role in molding the genomes of breast cancers and have been shown to be clinically useful for prognostic and therapeutic purposes. However, our knowledge of intra-tumoral genetic heterogeneity of this important class of somatic alterations is limited. Here, using single-cell sequencing, we comprehensively map out the facets of copy number alteration heterogeneity in a cohort of breast cancer tumors. Ou/var/www/html/elife/12-05-2020/backup/r analyses reveal: genetic heterogeneity of non-tumor cells (i.e. stroma) within the tumor mass; the extent to which copy number heterogeneity impacts breast cancer genomes and the importance of both the genomic location and dosage of sub-clonal events; the pervasive nature of genetic heterogeneity of chromosomal amplifications; and the association of copy number heterogeneity with clinical and biological parameters such as polyploidy and estrogen receptor negative status. Our data highlight the power of single-cell genomics in dissecting, in its many forms, intra-tumoral genetic heterogeneity of CNAs, the magnitude with which CNA heterogeneity affects the genomes of breast cancers, and the potential importance of CNA heterogeneity in phenomena such as therapeutic resistance and disease relapse.

Virus-Like Particles in a Human Breast Cancer: Structural Similarity to Previously Reported Particles

1973 ◽  
Vol 31 ◽  
pp. 378-379
Author(s):  
G. Kasnic ◽  
S. E. Stewart ◽  
C. Urbanski
Keyword(s):  
Breast Cancer ◽  
Biological Activity ◽  
Human Breast Cancer ◽  
Osteogenic Sarcoma ◽  
Human Tumor ◽  
Structural Similarity ◽  
Cell Tumor ◽  
Human Breast ◽  
Human Tumor Cell ◽  
Type Particle

We have reported the maturation of an intracisternal A-type particle in murine plasma cell tumor cultures and three human tumor cell cultures (rhabdomyosarcoma, lung adenocarcinoma, and osteogenic sarcoma) after IUDR-DMSO activation. In all of these studies the A-type particle seems to develop into a form with an electron dense nucleoid, presumably mature, which is also intracisternal. A similar intracisternal A-type particle has been described in leukemic guinea pigs. Although no biological activity has yet been demonstrated for these particles, on morphologic grounds, and by the manner in which they develop within the cell, they may represent members of the same family of viruses.

Further Ultrastructural Observations on Metastatic Nodules of Human Breast Cancer

1968 ◽  
Vol 26 ◽  
pp. 224-225
Author(s):  
John L. Swedo ◽  
R. W. Talley ◽  
John H. L. Watson
Keyword(s):  
Breast Cancer ◽  
Human Breast Cancer ◽  
Estrogen Therapy ◽  
Specimen Preparation ◽  
Human Breast ◽  
Autophagic Vacuoles ◽  
Previous Communication ◽  
Linear Profiles ◽  
Metastatic Nodule

Since the report, which described the ultrastructure of a metastatic nodule of human breast cancer after estrogen therapy, additional ultrastructural observations, including some which are correlative with pertinent findings in the literature concerning mycoplasmas, have been recorded concerning the same subject. Specimen preparation was identical to that in.The mitochondria possessed few cristae, and were deteriorated and vacuolated. They often contained particulates and fibrous structures, sometimes arranged in spindle-shaped bundles, Fig. 1. Another apparent aberration was the occurrence, Fig. 2 (arrows) of linear profiles of what seems to be SER, which lie between layers of RER, and are often recognizably continuous with them.It was noted that the structure of the round bodies, interpreted as within autophagic vacuoles in the previous communication, and of vesicular bodies, described morphologically closely resembled those of some mycoplasmas. Specifically, they simulated or reflected the various stages of replication reported for mycoplasmas grown on solid nutrient. Based on this observation, they are referred to here as “mycoplasma-like” structures, in anticipation of confirmatory evidence from investigations now in progress.

The proliferation of breast cancer cells are inhibited by the human intrabody targeting cyclinD1

2010 ◽  
Vol 34 (8) ◽  
pp. S49-S49
Author(s):  
Lei Wang ◽  
Xun Zhou ◽  
Lihong Zhou ◽  
Yong Chen ◽  
Xun Zhu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells
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