A Practical Approach for Targeting Structural Variants Genome-wide in Plasma Cell-free DNA.

Interrogating plasma cell-free DNA (cfDNA) to detect cancer offers promise; however, no current tests scan structural variants (SVs) throughout the genome. Here, we report a simple molecular workflow to enrich a tumorigenic SV (DNA palindromes/fold-back inversions) that often demarcates genomic amplification and its feasibility for cancer detection by combining low-throughput next-generation sequencing with automated machine learning (Genome-wide Analysis of Palindrome Formation, GAPF-seq). Tumor DNA signal manifested as skewed chromosomal distributions of high-coverage 1-kb bins (HCBs), differentiating 39 matched breast tumor DNA from normal DNA with an average AUC of 0.

A Practical Approach for Targeting Structural Variants Genome-wide in Plasma Cell-free DNA.

Plasma cell-free DNA (cfDNA) is a promising source of gene mutations for cancer detection by liquid biopsy. However, no current tests interrogate chromosomal structural variants (SVs) genome-wide. Here, we report a simple molecular and sequencing workflow called Genome-wide Analysis of Palindrome Formation (GAPF-seq) to probe DNA palindromes, a type of SV that often demarcates gene amplification.

The applications of plasma cell-free DNA in cancer detection: Implications in the management of breast cancer patients.

Liquid biopsy probes DNA, RNA, and proteins in body fluids for cancer detection and is one of the most rapidly developing areas in oncology. Tumor-derived DNA (circulating tumor DNA, ctDNA) in the context of cell-free DNA (cfDNA) in blood has been the main target for its potential utilities in cancer detection. Liquid biopsy can report tumor burden in real-time without invasive interventions, and would be feasible for screening tumor types that lack standard-of-care screening approaches.

The fragility of a structurally diverse duplication block triggers recurrent genomic amplification.

The human genome contains hundreds of large, structurally diverse blocks that are insufficiently represented in the reference genome and are thus not amenable to genomic analyses. Structural diversity in the human population suggests that these blocks are unstable in the germline; however, whether or not these blocks are also unstable in the cancer genome remains elusive. Here we report that the 500 kb block called KRTAP_region_1 (KRTAP-1) on 17q12-21 recurrently demarcates the amplicon of the ERBB2 (HER2) oncogene in breast tumors.

Plasminogen activator inhibitor-2 (PAI-2) overexpression supports bladder cancer development in PAI-1 knockout mice in N-butyl-N- (4-hydroxybutyl)-nitrosamine- induced bladder cancer mouse model.

Background: Accumulating evidence suggests that plasminogen activator inhibitor-1 (PAI-1) plays an important role in bladder tumorigenesis by regulating cell cycle. However, it remains unclear whether and how inhibition of PAI-1 suppresses bladder tumorigenesis.

Methods: To elucidate the therapeutic effect of PAI-1 inhibition, we tested its tumorigenicity in PAI-1 knockout (KO) mice exposed to a known bladder carcinogen.

Diagnostic significance of intratumoral CD8+ tumor-infiltrating lymphocytes in medullary carcinoma.

Invasive ductal carcinomas of breast with marked stromal lymphocytic infiltration have come to be classified as lymphocyte-predominant breast cancer (LPBC) because it obtains high pathological complete response rates with neoadjuvant chemotherapy. Medullary carcinoma (MC), which is independent from LPBC, is a rare histological subtype of invasive breast carcinoma accompanied by abundant lymphoplasmacytic infiltration as LPBC. Although MC shows marked cellular and structural atypia, it usually has a favorable outcome.

Ki67 expression and the effect of neo-adjuvant chemotherapy on luminal HER2-negative breast cancer.

Background: Patients with luminal HER2-negative tumours have a favourable prognosis. However, there is a subpopulation in which poorer outcomes are obtained with endocrine therapy alone. This subpopulation is considered to benefit from chemotherapy.