Histone variants, present in various cell types and tissues, are known to exhibit different functions. For example, histone H3.3 and H2A.Z are both involved in gene expression regulation, whereas H2A.X is a specific variant that responds to DNA double-strand breaks. In this study, we characterized H4G, a novel hominidae-specific histone H4 variant. We found that H4G is expressed in a variety of human cell lines and exhibit tumor-stage dependent overexpression in tissues from breast cancer patients. We found that H4G localized primarily to the nucleoli of the cell nucleus. This localization was controlled by the interaction of the alpha-helix 3 of the histone fold motif with a histone chaperone, nucleophosmin 1. In addition, we found that modulating H4G expression affects rRNA expression levels, protein synthesis rates and cell-cycle progression. Our data suggest that H4G expression alters nucleolar chromatin in a way that enhances rDNA transcription in breast cancer tissues.

Breast cancer is one of the most common types of cancer and is the leading cause of cancer-related death. Diagnosis of breast cancer is based on the evaluation of pathology slides. In the era of digital pathology, these slides can be converted into digital whole slide images (WSIs) for further analysis. However, due to their sheer size, digital WSIs diagnoses are time consuming and challenging. In this study, we present a lightweight architecture that consists of a bilinear structure and MobileNet-V3 network, bilinear MobileNet-V3 (BM-Net), to analyze breast cancer WSIs. We utilized the WSI dataset from the ICIAR2018 Grand Challenge on Breast Cancer Histology Images (BACH) competition, which contains four classes: normal, benign, in situ carcinoma, and invasive carcinoma. We adopted data augmentation techniques to increase diversity and utilized focal loss to remove class imbalance. We achieved high performance, with 0.88 accuracy in patch classification and an average 0.71 score, which surpassed state-of-the-art models. Our BM-Net shows great potential in detecting cancer in WSIs and is a promising clinical tool.

In 1963, Margoliash discovered the unexpected genetic equidistance result after comparing cytochrome c sequences from different species. This finding, together with the hemoglobin analyses of Zuckerkandl and Pauling in 1962, directly inspired the ad hoc molecular clock hypothesis. Unfortunately, however, many biologists have since mistakenly viewed the molecular clock as a genuine reality, which in turn inspired Kimura, King, and Jukes to propose the neutral theory of molecular evolution. Many years of studies have found numerous contradictions to the theory, and few today believe in a universal constant clock. What is being neglected, however, is that the failure of the molecular clock hypothesis has left the original equidistance result an unsolved mystery. In recent years, we fortuitously rediscovered the equidistance result, which remains unknown to nearly all researchers. Incorporating the proven virtues of existing evolutionary theories and introducing the novel concept of maximum genetic diversity, we proposed a more complete hypothesis of evolutionary genetics and reinterpreted the equidistance result and other major evolutionary phenomena. The hypothesis may rewrite molecular phylogeny and population genetics and solve major biomedical problems that challenge the existing framework of evolutionary biology.

Stress granules are non-membranous cytoplasmic foci induced by various stress conditions. It is a protective strategy used by cells to suppress overall translation during stress. In cancer cells, it was thought that the formation of stress granules could protect them from apoptosis and induces resistance towards anti-cancer drugs or radiation treatment which makes the stress granules a potential target for cancer treatment. However, most of our understanding of stress granules are still in the stage of molecular and cell biology, and a transitional gap for its actual effect on clinical settings remains. In this review, we summarize the mechanism and effect of stress granules formation in cancer and try to illuminate its potential applications in cancer therapy, using breast cancer as an example.

Regulators of histone acetylation are promising epigenetic targets for therapy in breast cancer. In this study, we comprehensively analyzed the expression of histone acetylation modulator genes in breast cancer using TCGA data sources. A gene signature composed of eight histone acetylation modulators (HAMs) was found to be effective for the classification and prognosis of breast cancers, especially in the HER2-enriched and basal-like molecular subtypes. The eight genes consist of two histone acetylation writers (GTF3C4 and CLOCK), two erasers (HDAC2 and SIRT7) and four readers (BRD4, BRD7, SP100, and BRWD3). Both histone acetylation writer genes and eraser genes were found to be differentially expressed between the two groups indicating a close relationship exists between overall histone acetylation level and prognosis of breast cancer in HER2-enriched and basal-like breast cancer.

Apocrine carcinoma is a rare subtype of invasive ductal breast cancer that shows apocrine differentiation and largely triple-negative immunohistology. Triple-negative breast cancers are known to have more aggressive clinical courses. However, unlike most other subtypes, it is reported that triple-negative apocrine carcinoma (TNAC) has a better prognosis. Due to the scarcity of reported studies, our knowledge regarding its clinical behavior, prognosis and response to therapy is very limited. In this study, we retrospectively retrieved 41 triple-negative apocrine carcinoma cases from our breast cancer database, with an average follow-up of 32.8 months. It was found that TNAC had a poorer response to neoadjuvant therapy but a better prognosis than other nonapocrine types of triple-negative breast cancer. Meanwhile, TNAC has a low proliferative nature, as indicated by its low Ki-67 index. An updated analysis of the Surveillance, Epidemiology, and End Results database showed that chemotherapy did not improve breast-cancer-specific survival in TNAC patients. Our results suggest that TNAC is a special subtype of triple-negative breast cancer with a better short-term prognosis despite poor response to neoadjuvant chemotherapy.