scholarly journals Genetic characterization of colorectal cancer using a next generation sequencing approach to identify a specific pattern of somatic alterations in tumors arising from different anatomic sites

2016 ◽  
Author(s):  
Carmelo Laudanna ◽  
Gianluca Santamaria ◽  
Simona Migliozzi ◽  
Duarte Mendes Oliveira ◽  
Donatella Malanga ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Copy Number ◽  
Treatment Options ◽  
Copy Number Variations ◽  
Specific Pattern ◽  
Surgical Approaches ◽  
Anatomical Location ◽  
Molecular Alterations ◽  
Somatic Alterations ◽  
Novel Biomarkers

Colorectal cancer (CRC) is the third leading cause of cancer-related deaths worldwide, with nearly 1.4 million new cases diagnosed in 2012. CRC results from the accumulation of multiple genetic and epigenetic aberrations. Tumor localization in the large intestine tract determines different surgical approaches and treatment options. Considering the heterogeneous nature of these tumors we hypothesized that different patterns of molecular alterations could be associated with a specific anatomical location. To identify distinct genomic alterations (e.g, copy number variations and mutations) associated to different CRC anatomical sites we sequenced 32 CRCs samples from different location (right-sided, left-sided etc.) using the Ion AmpliSeq™ Comprehensive Cancer Panel that covered the whole coding sequence of 409 tumor suppressor genes and oncogenes frequently altered in cancer. Interestingly left-sided tumors were generally more altered respect to right-sided ones. Cluster analysis of all samples allowed the identification of 21-gene core that were significantly mutated in all sample groups. As expected, KRAS and APC mutations were frequently in the tumors resected from different anatomical localizations. Unsupervised analysis of copy number variations reveals a core of 160-gene significantly altered. In addition to the expected SRC, MYC and CEBPA, we found interestingly genes in validation status. Despite missing a significant number of cases, gene panel provides a solid alternative approach to WES in order to characterize a signature of alterations correlated with CRC tumor and the identification of novel biomarkers in colorectal carcinoma that could be used as potential clinical target.

scholarly journals Genetic characterization of colorectal cancer using a next generation sequencing approach to identify a specific pattern of somatic alterations in tumors arising from different anatomic sites

2016 ◽  
Author(s):  
Carmelo Laudanna ◽  
Gianluca Santamaria ◽  
Simona Migliozzi ◽  
Duarte Mendes Oliveira ◽  
Donatella Malanga ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Copy Number ◽  
Treatment Options ◽  
Copy Number Variations ◽  
Specific Pattern ◽  
Surgical Approaches ◽  
Anatomical Location ◽  
Molecular Alterations ◽  
Somatic Alterations ◽  
Novel Biomarkers

Colorectal cancer (CRC) is the third leading cause of cancer-related deaths worldwide, with nearly 1.4 million new cases diagnosed in 2012. CRC results from the accumulation of multiple genetic and epigenetic aberrations. Tumor localization in the large intestine tract determines different surgical approaches and treatment options. Considering the heterogeneous nature of these tumors we hypothesized that different patterns of molecular alterations could be associated with a specific anatomical location. To identify distinct genomic alterations (e.g, copy number variations and mutations) associated to different CRC anatomical sites we sequenced 32 CRCs samples from different location (right-sided, left-sided etc.) using the Ion AmpliSeq™ Comprehensive Cancer Panel that covered the whole coding sequence of 409 tumor suppressor genes and oncogenes frequently altered in cancer. Interestingly left-sided tumors were generally more altered respect to right-sided ones. Cluster analysis of all samples allowed the identification of 21-gene core that were significantly mutated in all sample groups. As expected, KRAS and APC mutations were frequently in the tumors resected from different anatomical localizations. Unsupervised analysis of copy number variations reveals a core of 160-gene significantly altered. In addition to the expected SRC, MYC and CEBPA, we found interestingly genes in validation status. Despite missing a significant number of cases, gene panel provides a solid alternative approach to WES in order to characterize a signature of alterations correlated with CRC tumor and the identification of novel biomarkers in colorectal carcinoma that could be used as potential clinical target.

scholarly journals Carcinosarcoma of the prostate: case report with molecular and histological characterization

2018 ◽  
Vol 33 (4) ◽  
pp. 540-544 ◽  
Author(s):  
Samanta Salvi ◽  
Valentina Casadio ◽  
Filippo Martignano ◽  
Giorgia Gurioli ◽  
Maria Maddalena Tumedei ◽  
...  
Keyword(s):  
Copy Number Variation ◽  
Copy Number ◽  
Copy Number Variations ◽  
Molecular Characteristics ◽  
Glutathione S Transferase ◽  
Molecular Alterations ◽  
Positive Expression ◽  
Molecular Pattern ◽  
Programmed Death ◽  
Number Variation

Background: We report a case of prostatic carcinosarcoma, a rare variant of prostatic cancer, which is composed of a mixture of epithelial and mesenchymal components with a generally poor outcome. Aims and methods: We aim to identify molecular alterations, in particular copy number variations of AR and c -MYC genes, methylation and expression of glutathione S-transferase P1 (GSTP1), programmed death-ligand 1 (PD-L1), AR, and phosphorylated AR expression. Results: We found a distinct molecular pattern between adenocarcinoma and carcinosarcoma, which was characterized by high AR copy number variation gain; positive expression of PD-L1, AR, and phosphorylated AR; low espression of GSTP1 in epithelial component. The sarcomatoid component had a lower gain of the AR gene, and no expression of PD-L1, AR, phosphorylated AR, or GSTP1. Both components had a gain of c-MYC copy number variation. Conclusions: Our findings suggest that carcinosarcoma has specific molecular characteristics that could be indicative for early diagnosis and treatment selection.

scholarly journals PD-L1 Expression Predicts a Distinct Prognosis in Krukenberg Tumor with Corresponding Origins

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Haiyan Tai ◽  
Qin Yang ◽  
Zhiyong Wu ◽  
Su’an Sun ◽  
Rui Cao ◽  
...  
Keyword(s):  
T Cell ◽  
Copy Number ◽  
Treatment Options ◽  
Copy Number Variations ◽  
Signet Ring Cell ◽  
Krukenberg Tumor ◽  
Gastrointestinal Carcinoma ◽  
Primary Tumors ◽  
Signet Ring Cell Adenocarcinoma ◽  
Programmed Death

Krukenberg tumor (KT) is an uncommon ovarian metastatic signet-ring cell adenocarcinoma that mostly metastasizes from gastrointestinal carcinoma. Optimal treatment options for KTs are limited. Programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors have shown remarkable activity in clinical trials for metastatic tumors. Here, we evaluated PD-L1 expression and T cell infiltration in KTs and their corresponding primary tumors. Positive tumor PD-L1 expression was detected in 9 (25.7%) KTs from gastric carcinomas (GCs) and in 20 (66.7%) KTs from colorectal carcinomas (CRCs). Patient survival was assessed according to the PD-L1 status and CD8+ T cell density. Positive tumor PD-L1 expression in KTs from GCs was associated with poor prognosis. In contrast, positive tumor PD-L1 expression in KTs from CRCs was associated with an improved prognosis. We analyzed copy number variations of the PD-L1 gene in KTs. PD-L1 expression was higher in cases with copy number gains. The T cell densities within KTs and their corresponding primary tumors were compared. The densities of CD8+ T cells correlated significantly between the primary tumors and KTs from the same case. Taken together, the research further highlighted targets for immune-based therapy in KTs from GCs and CRCs.

scholarly journals Copy number variations primed lncRNAs deregulation contribute to poor prognosis in colorectal cancer

Aging ◽  
2019 ◽  
Vol 11 (16) ◽  
pp. 6089-6108 ◽  
Author(s):  
Huimin Liu ◽  
Xiaoyu Gu ◽  
Guihua Wang ◽  
Ying Huang ◽  
Shaoqing Ju ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Copy Number ◽  
Poor Prognosis ◽  
Copy Number Variations

scholarly journals New Regions With Molecular Alterations in a Rare Case of Insulinomatosis: Case Report With Literature Review

2021 ◽  
Vol 12 ◽  
Author(s):  
Kirill Anoshkin ◽  
Ivan Vasilyev ◽  
Kristina Karandasheva ◽  
Mikhail Shugay ◽  
Valeriya Kudryavtseva ◽  
...  
Keyword(s):  
Molecular Genetics ◽  
Copy Number ◽  
Rare Case ◽  
Point Mutations ◽  
Copy Number Variations ◽  
Copy Number Alterations ◽  
Β Cells ◽  
Molecular Alterations ◽  
Number Of Genes ◽  
The Moment

Insulinomatosis is characterized by monohormonality of multiple macro-tumors and micro-tumors that arise synchronously and metachronously in all regions of the pancreas, and often recurring hypoglycemia. One of the main characteristics of insulinomatosis is the presence of insulin-expressing monohormonal endocrine cell clusters that are exclusively composed of proliferating insulin-positive cells, are less than 1 mm in size, and show solid islet-like structure. It is presumed that insulinomatosis affects the entire population of β-cells. With regards to molecular genetics, this phenomenon is not related to mutation in MEN1 gene and is more similar to sporadic benign insulinomas, however, at the moment molecular genetics of this disease remains poorly investigated. NGS sequencing was performed with a panel of 409 cancer-related genes. Results of sequencing were analyzed by bioinformatic algorithms for detecting point mutations and copy number variations. DNA copy number variations were detected that harbor a large number of genes in insulinoma and fewer genes in micro-tumors. qPCR was used to confirm copy number variations at ATRX, FOXL2, IRS2 and CEBPA genes. Copy number alterations involving FOXL2, IRS2, CEBPA and ATRX genes were observed in insulinoma as well as in micro-tumors samples, suggesting that alterations of these genes may promote malignization in the β-cells population.

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