Biology subjects

Adamczyk, A.

Publications and source records attributed to Adamczyk, A..

3 recordsLinked to original sources

bioRxiv2025

Statistical and Evolutionary Analysis of Sequenced DNA from Breast Cancer FFPE Specimens

BackgroundDespite the introduction of instant freezing of tumor specimens, formalin-fixed paraffin-embedded (FFPE) blocks of tissue are still commonplace in clinical practice and constitute an important reference for genetic epidemiology of cancer. We carried out a study of a collection of breast tumors paired with lymph-node metastases and analyzed using advanced computational methods, to determine how much information can be obtained from mid-depth whole-exome bulk DNA sequencing. MethodsWe gathered 15 paired (primary and an involved lymph node) excised breast tumors of different molecular subtypes (HER2+, triple negative, luminal A and luminal B HER2-), from the National Research Institute of Oncology, Krakow (Poland) Branch. FFPE specimens contained typical artifacts, manifesting themselves in spurious DNA variant calls. We used several bioinformatics tools to remove the artifacts and analyzed the exomic data, using both commercial and original in-house computational techniques. ResultsWe used several of recent bioinformatics tools to remove the FFPE artifacts and found a serious dispersal of outcomes. After calibration, a series of analyses was performed, including copy number study, resulting in ploidy levels ranging from 1 to 5 (average of 2.5). Positive association was found between the frequency of oncogenes relative to tumor suppressor genes and DNA copy number. In addition, we carried out analyses of the clonal structure of the data using original computational methods based on evolutionary modeling. Interesting results concerning clonal structure, early tumor expansion, and interdependence of the primary tumor and lymph node metastases have been obtained. ConclusionsDespite the imperfections of the FFPE data, many important features of molecular evolution of tumor DNA can be recovered from routine clinical samples.

evolutionary biology↗

bioRxiv2022

Acute Cytomegalovirus Infection Modulates the Intestinal Microbiota and Targets Intestinal Epithelial Cells

Primary and recurrent cytomegalovirus (CMV) infections frequently cause CMV colitis in immunocompromised as well as inflammatory bowel disease (IBD) patients. Additionally, colitis occasionally occurs upon primary CMV infection in patients who are apparently immunocompetent. In both cases, the underlying pathophysiologic mechanisms are largely elusive - in part due to the lack of adequate access to specimens. We employed the mouse cytomegalovirus (MCMV) model to probe into the association between CMV and colitis. During acute primary MCMV infection of immunocompetent mice, the gut microbial composition was affected within the first 5 days post-infection as manifested by an altered ratio of the Firmicutes to Bacteroidetes phyla. Interestingly, these microbial changes incited with high-titer MCMV replication in the colon, mild crypt necrosis and increased colonic pro-inflammatory cytokine levels. Further analyses revealed that murine and human intestinal epithelial cell line as well as primary intestinal crypt cells/ organoids represent direct targets of CMV accompanied by increased cell mortality upon infection. Accordingly, in vivo MCMV infection disrupted the intestinal epithelial barrier and increased apoptosis of intestinal epithelial cells. In summary, our data show that CMV induces colitis in immunocompetent hosts by altering the intestinal homeostasis.

microbiology↗

bioRxiv2021

Comprehensive cancer-oriented biobanking resource of human samples for studies of post-zygotic genetic variation involved in cancer predisposition

The progress in translational cancer research relies on access to well-characterized samples from a representative number of patients and controls. The rationale behind our biobanking are explorations of post-zygotic pathogenic gene variants, especially in non-tumoral tissue, which might predispose to cancers. The targeted diagnoses are carcinomas of the breast (via mastectomy or breast conserving surgery), colon and rectum, prostate, and urinary bladder (via cystectomy or transurethral resection), exocrine pancreatic carcinoma as well as metastases of colorectal cancer to the liver. The choice was based on the high incidence of these cancers and/or frequent fatal outcome. We also collect age-matched normal controls. Our still ongoing collection originates from five clinical centers and after nearly 2-year cooperation reached 1711 patients and controls, yielding a total of 23226 independent samples, with an average of 74 donors and 1010 samples collected per month. The predominant diagnosis is breast carcinoma, with 933 donors, followed by colorectal carcinoma (383 donors), prostate carcinoma (221 donors), bladder carcinoma (81 donors), exocrine pancreatic carcinoma (15 donors) and metachronous colorectal cancer metastases to liver (14 donors). Forty percent of the total sample count originates from macroscopically healthy cancer-neighboring tissue, while contribution from tumors is 12%, which adds to the uniqueness of our collection for cancer predisposition studies. Moreover, we developed two program packages, enabling registration of patients, clinical data and samples at the participating hospitals as well as the central system of sample/data management at coordinating center. The approach used by us may serve as a model for dispersed biobanking from multiple satellite hospitals. Our biobanking resource ought to stimulate research into genetic mechanisms underlying the development of common cancers. It will allow all available "-omics" approaches on DNA-, RNA-, protein- and tissue levels to be applied. The collected samples can be made available to other research groups.

cancer biology↗