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M. Teresiak

Bio: M. Teresiak is an academic researcher from National Institutes of Health. The author has contributed to research in topics: Cancer & Melanoma. The author has an hindex of 5, co-authored 15 publications receiving 13474 citations.
Topics: Cancer, Melanoma, Adenocarcinoma, Carcinoma, Exome

Papers
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Journal ArticleDOI
04 Oct 2012-Nature
TL;DR: The ability to integrate information across platforms provided key insights into previously defined gene expression subtypes and demonstrated the existence of four main breast cancer classes when combining data from five platforms, each of which shows significant molecular heterogeneity.
Abstract: We analysed primary breast cancers by genomic DNA copy number arrays, DNA methylation, exome sequencing, messenger RNA arrays, microRNA sequencing and reverse-phase protein arrays. Our ability to integrate information across platforms provided key insights into previously defined gene expression subtypes and demonstrated the existence of four main breast cancer classes when combining data from five platforms, each of which shows significant molecular heterogeneity. Somatic mutations in only three genes (TP53, PIK3CA and GATA3) occurred at >10% incidence across all breast cancers; however, there were numerous subtype-associated and novel gene mutations including the enrichment of specific mutations in GATA3, PIK3CA and MAP3K1 with the luminal A subtype. We identified two novel protein-expression-defined subgroups, possibly produced by stromal/microenvironmental elements, and integrated analyses identified specific signalling pathways dominant in each molecular subtype including a HER2/phosphorylated HER2/EGFR/phosphorylated EGFR signature within the HER2-enriched expression subtype. Comparison of basal-like breast tumours with high-grade serous ovarian tumours showed many molecular commonalities, indicating a related aetiology and similar therapeutic opportunities. The biological finding of the four main breast cancer subtypes caused by different subsets of genetic and epigenetic abnormalities raises the hypothesis that much of the clinically observable plasticity and heterogeneity occurs within, and not across, these major biological subtypes of breast cancer.

9,355 citations

Journal ArticleDOI
Adam J. Bass1, Vesteinn Thorsson2, Ilya Shmulevich2, Sheila Reynolds2  +254 moreInstitutions (32)
11 Sep 2014-Nature
TL;DR: A comprehensive molecular evaluation of 295 primary gastric adenocarcinomas as part of The Cancer Genome Atlas (TCGA) project is described and a molecular classification dividing gastric cancer into four subtypes is proposed.
Abstract: Gastric cancer was the world’s third leading cause of cancer mortality in 2012, responsible for 723,000 deaths1. The vast majority of gastric cancers are adenocarcinomas, which can be further subdivided into intestinal and diffuse types according to the Lauren classification2. An alternative system, proposed by the World Health Organization, divides gastric cancer into papillary, tubular, mucinous (colloid) and poorly cohesive carcinomas3. These classification systems have little clinical utility, making the development of robust classifiers that can guide patient therapy an urgent priority. The majority of gastric cancers are associated with infectious agents, including the bacterium Helicobacter pylori4 and Epstein–Barr virus (EBV). The distribution of histological subtypes of gastric cancer and the frequencies of H. pylori and EBV associated gastric cancer vary across the globe5. A small minority of gastric cancer cases are associated with germline mutation in E-cadherin (CDH1)6 or mismatch repair genes7 (Lynch syndrome), whereas sporadic mismatch repair-deficient gastric cancers have epigenetic silencing of MLH1 in the context of a CpG island methylator phenotype (CIMP)8. Molecular profiling of gastric cancer has been performed using gene expression or DNA sequencing9–12, but has not led to a clear biologic classification scheme. The goals of this study by The Cancer Genome Atlas (TCGA) were to develop a robust molecular classification of gastric cancer and to identify dysregulated pathways and candidate drivers of distinct classes of gastric cancer.

4,583 citations

Journal ArticleDOI
Rehan Akbani, Kadir C. Akdemir, B. Arman Aksoy1, Monique Albert1  +348 moreInstitutions (1)
18 Jun 2015-Cell
TL;DR: This clinicopathological and multi-dimensional analysis suggests that the prognosis of melanoma patients with regional metastases is influenced by tumor stroma immunobiology, offering insights to further personalize therapeutic decision-making.

2,337 citations

Journal Article
TL;DR: The BRCA2 mutations and AR expression in tumor tissue are independent adverse factors for MBC prognosis and presents at the earlier age compared with non-BRCA 2-related cancer, but do not differ with respect to other clinicopathological features.
Abstract: Purpose: Germline mutations of the BRCA2 gene are involved in the development of a considerable number of male breast cancer cases. Although phenotypic differences have been observed between sporadic and BRCA-related breast carcinomas, conflicting data exist on the differences in prognosis of women with hereditary and sporadic breast cancer. The purpose of the study was to investigate the prognostic value of BRCA2 status in male breast carcinoma (MBC). Experimental Design: We studied 43 male breast cancer patients, including 12 with BRCA2 mutations. Tumor samples were characterized immunohistochemically using antibodies to estrogen receptor, progesterone receptor, and androgen receptor (AR). Results: BRCA2-related tumors presented at the earlier age compared with sporadic tumors (P = 0.005). Patients positive and negative for BRCA2 mutations did not differ with respect to tumor size, lymph node involvement, histological grade, and sex hormone receptor status. Five-year disease-free survival (DFS) and overall survival (OS) were significantly decreased in BRCA2-positive patients (67% versus 28% for BRCA2-negative versus positive patients, respectively, P = 0.017 for DFS; 86% versus 25%, P = 0.006 for OS). Shorter survival was also correlated with expression of AR in tumor tissue (74% versus 33% for patients with tumors staining negatively and positively for AR, P = 0.029 for DFS; 71% versus 57%, P = 0.05 for OS). Conclusions: The BRCA2 mutations and AR expression in tumor tissue are independent adverse factors for MBC prognosis. BRCA2-related MBC presents at the earlier age compared with non-BRCA2-related cancer, but do not differ with respect to other clinicopathological features.

81 citations

Journal ArticleDOI
TL;DR: There was a correlation between survival time and nm23 antigen expression and the thickness of melanoma, as measured by the Breslow method in mm, and it was concluded that there were correlations between patient survival or death and the histological type of Superficial Spreading Melanoma Malignum.

8 citations


Cited by
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Journal ArticleDOI
TL;DR: A practical guide to the analysis and visualization features of the cBioPortal for Cancer Genomics, which makes complex cancer genomics profiles accessible to researchers and clinicians without requiring bioinformatics expertise, thus facilitating biological discoveries.
Abstract: The cBioPortal for Cancer Genomics (http://cbioportal.org) provides a Web resource for exploring, visualizing, and analyzing multidimensional cancer genomics data. The portal reduces molecular profiling data from cancer tissues and cell lines into readily understandable genetic, epigenetic, gene expression, and proteomic events. The query interface combined with customized data storage enables researchers to interactively explore genetic alterations across samples, genes, and pathways and, when available in the underlying data, to link these to clinical outcomes. The portal provides graphical summaries of gene-level data from multiple platforms, network visualization and analysis, survival analysis, patient-centric queries, and software programmatic access. The intuitive Web interface of the portal makes complex cancer genomics profiles accessible to researchers and clinicians without requiring bioinformatics expertise, thus facilitating biological discoveries. Here, we provide a practical guide to the analysis and visualization features of the cBioPortal for Cancer Genomics.

10,947 citations

Journal ArticleDOI
TL;DR: This study showed that mismatch-repair status predicted clinical benefit of immune checkpoint blockade with pembrolizumab, and high somatic mutation loads were associated with prolonged progression-free survival.
Abstract: BackgroundSomatic mutations have the potential to encode “non-self” immunogenic antigens. We hypothesized that tumors with a large number of somatic mutations due to mismatch-repair defects may be susceptible to immune checkpoint blockade. MethodsWe conducted a phase 2 study to evaluate the clinical activity of pembrolizumab, an anti–programmed death 1 immune checkpoint inhibitor, in 41 patients with progressive metastatic carcinoma with or without mismatch-repair deficiency. Pembrolizumab was administered intravenously at a dose of 10 mg per kilogram of body weight every 14 days in patients with mismatch repair–deficient colorectal cancers, patients with mismatch repair–proficient colorectal cancers, and patients with mismatch repair–deficient cancers that were not colorectal. The coprimary end points were the immune-related objective response rate and the 20-week immune-related progression-free survival rate. ResultsThe immune-related objective response rate and immune-related progression-free survival ...

6,835 citations

Journal ArticleDOI
29 Mar 2013-Science
TL;DR: This work has revealed the genomic landscapes of common forms of human cancer, which consists of a small number of “mountains” (genes altered in a high percentage of tumors) and a much larger number of "hills" (Genes altered infrequently).
Abstract: Over the past decade, comprehensive sequencing efforts have revealed the genomic landscapes of common forms of human cancer. For most cancer types, this landscape consists of a small number of “mountains” (genes altered in a high percentage of tumors) and a much larger number of “hills” (genes altered infrequently). To date, these studies have revealed ~140 genes that, when altered by intragenic mutations, can promote or “drive” tumorigenesis. A typical tumor contains two to eight of these “driver gene” mutations; the remaining mutations are passengers that confer no selective growth advantage. Driver genes can be classified into 12 signaling pathways that regulate three core cellular processes: cell fate, cell survival, and genome maintenance. A better understanding of these pathways is one of the most pressing needs in basic cancer research. Even now, however, our knowledge of cancer genomes is sufficient to guide the development of more effective approaches for reducing cancer morbidity and mortality.

6,441 citations

Journal ArticleDOI
TL;DR: This review summarizes the clinical efficacy, perspectives, and future challenges of using PD-1/PD-L1-directed antibodies in the treatment of breast cancer.
Abstract: Immune checkpoint inhibition represents a major recent breakthrough in the treatment of malignant diseases including breast cancer. Blocking the programmed death receptor-1 (PD-1) and its ligand, PD-L1, has shown impressive antitumor activity and may lead to durable long-term disease control, especially in the triple-negative subtypes of breast cancer (TNBC). Although immune checkpoint blockade is generally well tolerated, specific immune-related adverse events (irAEs) may occur. This review summarizes the clinical efficacy, perspectives, and future challenges of using PD-1/PD-L1-directed antibodies in the treatment of breast cancer.

5,777 citations