scholarly journals Cancer/Testis genes are predictive of breast tumor subtypes

2021 ◽  
Author(s):  
Marthe Laisne ◽  
Sarah Benlarama ◽  
Andre Nicolas ◽  
Lounes Djerroudi ◽  
Nikhil Gupta ◽  
...  
Keyword(s):  
De Novo ◽  
Breast Tumors ◽  
Normal Breast ◽  
Dna Demethylation ◽  
New Approach ◽  
Tumor Subtypes ◽  
Response To Chemotherapy ◽  
Germline Genes ◽  
Her 2 ◽  
Cancer Testis

Breast cancer is the most prevalent type of cancer in women worldwide. Within breast tumors, the basal-like subtype has the worst prognosis and no dedicated therapy, therefore new tools to understand, detect, and treat these tumors are needed. Certain germline genes are re-expressed in tumors, and constitute the Cancer/Testis genes; their misexpression has diagnostic and therapeutic applications. Here, we designed a new approach to examine Cancer/Testis gene misexpression in breast tumors. We identify several new markers in Luminal and HER-2 positive tumors, some of which predict response to chemotherapy. We then use machine learning to identify the 2 Cancer/Testis genes most associated with basal-like breast tumors: HORMAD1 and CT83. We show that these genes are expressed by tumor cells but not the microenvironment, and that they are not expressed by normal breast progenitors, in other words their activation occurs de novo. We find these genes are epigenetically repressed by DNA methylation, and that their activation upon DNA demethylation is irreversible, providing a memory of past epigenetic disturbances. Basal-like tumors expressing both genes have a poorer outcome than tumors expressing either gene alone or neither gene. Therefore, these findings suggest a potential synergistic effect between Cancer/Testis genes in basal breast tumors; these findings have consequences for the understanding, diagnosis, and therapy of the breast tumors with the worse outcomes.

scholarly journals Immunohistochemiluminescence Detection: A Quantitative Tool in Breast Cancer HER-2 Status Evaluation

2013 ◽  
Vol 34 (5) ◽  
pp. 373-377 ◽  
Author(s):  
Moacyr Jesus Barreto de Melo Rêgo ◽  
Marina Ferraz Cordeiro ◽  
Carmelita de Lima Bezerra Cavalcanti ◽  
Luiz Bezerra de Carvalho Junior ◽  
Eduardo Isidoro Carneiro Beltrão
Keyword(s):  
Breast Cancer ◽  
Ductal Carcinoma ◽  
Breast Tumors ◽  
Normal Breast ◽  
Normal Tissues ◽  
Breast Invasive Ductal Carcinoma ◽  
Her 2 ◽  
Status Differences ◽  
Quantitative Tool ◽  
Acridinium Ester

Her-2 status evaluation in breast cancer has prognostic and treatment response value but its interobserver variation among pathologists is a problem since it is not quantitatively assayed. This study presents an immunohistochemiluminescence method to quantify Her-2 in breast cancer. Anti-Her-2 antibody was conjugated to acridinium ester (AE) and used to evaluate/quantify Her-2 status in breast Invasive Ductal Carcinoma (IDC,n= 50) comparing with traditional immunohistochemistry. Anti-HER-2-AE results were expressed in Relative Lights Units (RLU) and showed to be able to distinguish and quantify the differences between the three groups of Her-2 status. 3+ Her-2 status presented the highest RLU (246,982 × 103± 2.061 × 103) compared to 2+ (76,146 × 103± 0.290 × 103), negative (27,415 × 103± 1.445 × 103) and normal tissues (27,064 × 103± 2.060). Status differences were significant between 3+ and 2+ (p= 0.0025); 2+ and negative (p= 0.0003), and +3 and +1 (p= 0.0001) beside this, normal breast control RLU was 27,064 × 103± 2,060 × 103, similar to negative cases. Results showed that anti-HER-2-AE conjugate was effective in breast tumors Her-2 status evaluation, allowing its quantitative establishment to consequently decrease the subjectivity in prognostic and predictive information intrinsic to this test.

scholarly journals Pan-cancer characterization of lncRNA modifiers of immune microenvironment reveals clinically distinct de novo tumor subtypes

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Zicheng Zhang ◽  
Congcong Yan ◽  
Ke Li ◽  
Siqi Bao ◽  
Lei Li ◽  
...  
Keyword(s):  
Noncoding Rna ◽  
Immune Cell ◽  
De Novo ◽  
Solid Cancer ◽  
Immune Microenvironment ◽  
Cancer Subtypes ◽  
Tumor Subtypes ◽  
Cancer Immunity ◽  
Systems Immunology ◽  
Pan Cancer

AbstractThe emerging field of long noncoding RNA (lncRNA)-immunity has provided a new perspective on cancer immunity and immunotherapies. The lncRNA modifiers of infiltrating immune cells in the tumor immune microenvironment (TIME) and their impact on tumor behavior and disease prognosis remain largely uncharacterized. In the present study, a systems immunology framework integrating the noncoding transcriptome and immunogenomics profiles of 9549 tumor samples across 30 solid cancer types was used, and 36 lncRNAs were identified as modifier candidates underlying immune cell infiltration in the TIME at the pan-cancer level. These TIME lncRNA modifiers (TIL-lncRNAs) were able to subclassify various tumors into three de novo pan-cancer subtypes characterized by distinct immunological features, biological behaviors, and disease prognoses. Finally, a TIL-lncRNA-derived immune state index (TISI) that was reflective of immunological and oncogenic states but also predictive of patients’ prognosis was proposed. Furthermore, the TISI provided additional prognostic value for existing tumor immunological and molecular subtypes. By applying the TISI to tumors from different clinical immunotherapy cohorts, the TISI was found to be significantly negatively correlated with immune-checkpoint genes and to have the ability to predict the effectiveness of immunotherapy. In conclusion, the present study provided comprehensive resources and insights for future functional and mechanistic studies on lncRNA-mediated cancer immunity and highlighted the potential of the clinical application of lncRNA-based immunotherapeutic strategies in precision immunotherapy.

Pan-cancer evaluation of homologous repair deficiency somatic mutations and response to first-line anti-neoplastic therapy.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 10535-10535
Author(s):  
Jessica A Lavery ◽  
Samantha Brown ◽  
Gregory J. Riely ◽  
Philippe L. Bedard ◽  
Ben Ho Park ◽  
...  
Keyword(s):  
Somatic Mutations ◽  
De Novo ◽  
Stage Iv ◽  
Progression Free Survival ◽  
First Line ◽  
Major Mechanism ◽  
First Line Therapy ◽  
Oncogenic Mutation ◽  
Line Therapy ◽  
Response To Chemotherapy

10535 Background: Homologous recombination is a major mechanism of defective DNA repair, but it remains uncertain whether homologous repair deficient (HRD) tumors have favorable prognosis or are more/less likely to respond to treatment than tumors lacking such mutations. Objective: To determine whether lung (NSCLC) and colorectal (CRC) HRD+ tumors have better survival or response to chemotherapy than HRD- tumors. Methods: Patients with de novo stage IV NSCLC or CRC who had next generation sequencing (NGS) between 2015-2018 from one of four cancer centers were identified. Records were curated using the PRISSMM framework to ascertain treatment, overall survival (OS) and progression free survival based on imaging (PFS-I) and oncologists’ notes (PFS-M). Each NSCLC or CRC tumor was categorized as HRD+ if NGS revealed an oncogenic/likely oncogenic mutation in: ATM, BAP1, BARD1, BLM, BRCA1, BRCA2, BRIP1, CHEK2, FAM175A, FANCA, FANCC, NBN, PALB2, RAD50, RAD51, RAD51C, RTEL1, or MRE11A based on the OncoKB database. The tumor was categorized as HRD- if no oncogenic mutation in any of these genes was evident and HRD indeterminate (HRD?) if no mutation was identified but the panel did not include all genes. OS, PFS-I and PFS-M from start of first line therapy were reported by HRD status. The percentage with a good response to first line therapy (≥2x the median) and exceptional response (≥3x the median) was estimated for each endpoint. Results: For NSCLC 4% were HRD+, 59% HRD- and 37% HRD?. For CRC there were 5% HRD+, 60% HRD- and 35% HRD?. There were no significant differences for any survival endpoint between patients who were HRD+ vs HRD- in univariable analyses. The proportion of good and exceptional responders to first line systemic chemotherapy also did not vary by HRD status, though patients with HRD+ CRC were potentially more likely to be exceptional responders. Similarly, no differences between HRD+ and HRD- tumors were apparent for the subgroup receiving platinum containing therapy. Conclusions: NSCLC and CRC patients with somatic mutations in HRD oncogenic genes did not differ from patients lacking such a mutation with respect to OS or PFS. CRC patients with HRD+ tumors may be more likely to be exceptional responders, but sample sizes are limited. By May, the analysis will include breast and pancreatic cancer cases.[Table: see text]

scholarly journals Amino acids at the site of V kappa-J kappa recombination not encoded by germline sequences.

1987 ◽  
Vol 166 (3) ◽  
pp. 637-646 ◽  
Author(s):  
M Heller ◽  
J D Owens ◽  
J F Mushinski ◽  
S Rudikoff
Keyword(s):  
Heavy Chain ◽  
De Novo ◽  
Size Variation ◽  
Chain Gene ◽  
Gene Recombination ◽  
Heavy Chain Gene ◽  
Single Nucleotide ◽  
Reading Frame ◽  
Germline Genes ◽  
Unusual Amino Acid

Murine V kappa-J kappa recombination is characterized by a maintenance of size at the site of recombination and the use of nucleic acids found only in germline sequences. This is in contrast to heavy chain VH-D-JH assembly where random nucleotides are added at the recombination sites to produce considerable size variation, even though the heptamer/nonomer recombination sequences are identical in both kappa and heavy chain genes. We have examined the origin of an unusual amino acid, Ile, found at the site of V kappa-J kappa recombination in antigalactan antibodies, by sequence analysis of the corresponding rearranged and germline genes. Results indicate that the Ile codon can be generated by use of a single nucleotide 3' of the V kappa segment in combination with the second and third nucleotides of the first codon of J kappa 5 or J kappa 4. However, several antigalactan antibodies express Ile in combination with J kappa 2. An Ile codon cannot be generated by recombination in any reading frame between germline V kappa and J kappa 2 segments. These results suggest that the origin of the Ile codon in lines using J kappa 2 may represent a novel even in murine light chain assembly, possibly similar to the de novo addition of nucleotides observed in heavy chain gene recombination.

scholarly journals Intratumor heterogeneity defines treatment‐resistant HER 2+ breast tumors

2018 ◽  
Vol 12 (11) ◽  
pp. 1838-1855 ◽  
Author(s):  
Inga H. Rye ◽  
Anne Trinh ◽  
Anna B. Sætersdal ◽  
Daniel Nebdal ◽  
Ole Christian Lingjærde ◽  
...  
Keyword(s):  
Breast Tumors ◽  
Intratumor Heterogeneity ◽  
Treatment Resistant ◽  
Her 2

Macromolecular contrast media. A new approach for characterising breast tumors with MR-mammography

Der Radiologe ◽  
1997 ◽  
Vol 37 (9) ◽  
pp. 733-740 ◽  
Author(s):  
H. E. Daldrup ◽  
T. P. L. Roberts ◽  
A. Mühler ◽  
A. Gossmann ◽  
H. C. Roberts ◽  
...  
Keyword(s):  
Contrast Media ◽  
Breast Tumors ◽  
Mr Mammography ◽  
New Approach

In vivo1H MRS of normal breast and breast tumors using a dedicated double breast coil

1998 ◽  
Vol 8 (6) ◽  
pp. 1191-1197 ◽  
Author(s):  
Ingrid S. Gribbestad ◽  
Trond E. Singstad ◽  
Gunnar Nilsen ◽  
Hans E. Fjøsne ◽  
Terje Engan ◽  
...  
Keyword(s):  
Breast Tumors ◽  
Normal Breast ◽  
Breast Coil

scholarly journals Cancer-testis Antigen FATE1 Expression in Adrenocortical Tumors Is Associated with A Pervasive Autoimmune Response and Is A Marker of Malignancy in Adult, but Not Children, ACC

Cancers ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 689 ◽  
Author(s):  
Mabrouka Doghman-Bouguerra ◽  
Pascal Finetti ◽  
Nelly Durand ◽  
Ivy Zortéa S. Parise ◽  
Silviu Sbiera ◽  
...  
Keyword(s):  
Immune Response ◽  
Prognostic Indicator ◽  
Adult Patients ◽  
Autoimmune Response ◽  
Immune Response Gene ◽  
Cancer Testis Antigen ◽  
Adrenocortical Tumors ◽  
Response To Chemotherapy ◽  
Transcription Factor Target ◽  
Cancer Testis

The SF-1 transcription factor target gene FATE1 encodes a cancer-testis antigen that has an important role in regulating apoptosis and response to chemotherapy in adrenocortical carcinoma (ACC) cells. Autoantibodies directed against FATE1 were previously detected in patients with hepatocellular carcinoma. In this study, we investigated the prevalence of circulating anti-FATE1 antibodies in pediatric and adult patients with adrenocortical tumors using three different methods (immunofluorescence, ELISA and Western blot). Our results show that a pervasive anti-FATE1 immune response is present in those patients. Furthermore, FATE1 expression is a robust prognostic indicator in adult patients with ACC and is associated with increased steroidogenic and decreased immune response gene expression. These data can open perspectives for novel strategies in ACC immunotherapy.

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