The Mutational Spectrum of Pre- and Post-Neoadjuvant Chemotherapy Triple-Negative Breast Cancers.

The response of triple-negative breast cancer (TNBC) patients to pre-operative (neoadjuvant chemotherapy) is a critical factor of their outcome. To determine the effects of chemotherapy on the tumor genome and to identify mutations associated with chemoresistance and sensitivity, we performed whole exome sequencing on pre/post-chemotherapy tumors and matched lymphocytes from 26 patients. We observed great inter-tumoral heterogeneity with no gene mutated recurrently in more than four tumors besides TP53.

Incidence of Occult Breast Cancer in Carriers of BRCA1/2 or Other High-Penetrance Pathogenic Variants Undergoing Prophylactic Mastectomy: When is Sentinel Lymph Node Biopsy Indicated?

Background: This study sought to determine the likelihood of occult malignancy during risk-reducing mastectomy in high-penetrance pathogenic variant carriers to help refine axillary staging recommendations.

Methods: The authors performed a retrospective cohort study analyzing all female carriers of pathogenic variants in BRCA1/2, PALB2 or other genes who underwent prophylactic surgery at their institution between 2006 and 2021. Occult breast cancer was defined as the unanticipated presence of in situ or invasive malignancy on pathologic evaluation of prophylactic mastectomy specimens.

Reasons for delay in timely administration of adjuvant chemotherapy for patients with stage III colon cancer: a multicentre cohort study from the McGill University Department of Oncology.

Purpose: Adjuvant chemotherapy within 56 or 84 days following curative resection is globally accepted as the standard of care for stage III colon cancer as it has been associated with improved overall survival. Initiation of adjuvant chemotherapy within this time frame is therefore recommended by clinical practice guidelines, including the European Society for Medical Oncology. The objective of this study was to evaluate adherence to these clinical practice guidelines for patients with stage III colon cancer across the Rossy Cancer Network (RCN); a partnership of McGill University's Faculty of Medicine, McGill University Health Centre, Jewish General Hospital and St Mary's Hospital Center.

Investigating the causal role of MRE11A p.E506* in breast and ovarian cancer.

The nuclease MRE11A is often included in genetic test panels for hereditary breast and ovarian cancer (HBOC) due to its BRCA1-related molecular function in the DNA repair pathway. However, whether MRE11A is a true predisposition gene for HBOC is still questionable. We determined to investigate this notion by dissecting the molecular genetics of the c.

A Unique Morphological Phenotype in Chemoresistant Triple-Negative Breast Cancer Reveals Metabolic Reprogramming and PLIN4 Expression as a Molecular Vulnerability.

The major obstacle in successfully treating triple-negative breast cancer (TNBC) is resistance to cytotoxic chemotherapy, the mainstay of treatment in this disease. Previous preclinical models of chemoresistance in TNBC have suffered from a lack of clinical relevance. Using a single high dose chemotherapy treatment, we developed a novel MDA-MB-436 cell-based model of chemoresistance characterized by a unique and complex morphologic phenotype, which consists of polyploid giant cancer cells giving rise to neuron-like mononuclear daughter cells filled with smaller but functional mitochondria and numerous lipid droplets.

Biliary mucinous cystic neoplasm mimicking a hydatid cyst: a case report and literature review.

Background: Biliary mucinous cystic neoplasms are rare cystic lesions of the liver which carry pre-malignant potential. Given the scarcity of reports in the literature, they pose a considerable challenge to clinical management, particularly with regards to accurate pre-operative diagnosis.

Case Presentation: We present the case of a 37-year-old Tunisian woman who presented with subacute right upper quadrant pain and a large multi-loculated cystic lesion, most consistent with a hydatid cyst.

The role of nelarabine in the treatment of T-cell acute lymphoblastic leukemia: literature review and own experience.

Aim: The analysis of experience of nelarabine use in refractory/relapsed T-cell acute lymphoblastic leukemia (T-ALL) depending on the immunophenotype and the line of therapy.

Materials And Methods: All the patients with relapsed or refractory T-ALL aged from 0 to 18 years who received treatment with nelarabine as a part of the therapeutic element R6 were included in the study. For all patients a detailed immunological analysis of leukemia cells with discrimination of immunological variants TI, TII, TIII or TIV was performed.

Functionally Null Missense Mutation Associates Strongly with Ovarian Carcinoma.

RAD51D is a key player in DNA repair by homologous recombination (HR), and truncating variant carriers have an increased risk for ovarian cancer. However, the contribution of nontruncating variants to cancer predisposition remains uncertain. Using deep sequencing and case-control genotyping studies, we show that in French Canadians, the missense variant c.

The p53 status can influence the role of Sam68 in tumorigenesis.

The expression and activities of RNA binding proteins are frequently dysregulated in human cancer. Their roles, however, appears to be complex, with reports indicating both pro-tumorigenic and tumor suppressive functions. Here we show, using two classical mouse cancer models, that the role of KH-type RNA binding protein, Sam68, in tumor development can be influenced by the status of the p53 tumor suppressor.

A phenotype of IGFBP-3 knockout mice revealed by dextran sulfate-induced colitis.

Background And Aim: Insulin-like growth factor-1 (IGF-1) bioactivity has been shown to be attenuated by insulin-like growth factor binding protein-3 (IGFBP-3), one of six IGF-binding proteins. While prior work revealed no major phenotype associated with IGFBP-3 knockout mice, we explored the possibility that a phenotype could be revealed under specific conditions of gastrointestinal stress.

Methods: The dextran sodium sulfate (DSS) murine model of ulcerative colitis was used for this study.

Mesenchymal Bone Marrow-derived Stem Cells Transplantation in Patients with HCV Related Liver Cirrhosis.

Background And Aims: To evaluate the effect of intraparenchymal transplantation of mesenchymal bone marrow-derived stem cells (BMSCs) in patients with hepatitis C virus (HCV)-related liver cirrhosis (LC).

Methods: Mononuclear cells were isolated from patient bone marrow and were passaged several times in vitro in order to reach the required volume. Attributes of the BMSCs were evaluated by the presence of the surface markers CD105+, CD90+, and CD73+.

The Estrogen Receptor Cofactor SPEN Functions as a Tumor Suppressor and Candidate Biomarker of Drug Responsiveness in Hormone-Dependent Breast Cancers.

The treatment of breast cancer has benefitted tremendously from the generation of estrogen receptor-α (ERα)-targeted therapies, but disease relapse continues to pose a challenge due to intrinsic or acquired drug resistance. In an effort to delineate potential predictive biomarkers of therapy responsiveness, multiple groups have identified several uncharacterized cofactors and interacting partners of ERα, including Split Ends (SPEN), a transcriptional corepressor. Here, we demonstrate a role for SPEN in ERα-expressing breast cancers.

Germ line knockout of IGFBP-3 reveals influences of the gene on mammary gland neoplasia.

Insulin-like growth factor binding protein-3 (IGFBP-3) is an important carrier protein for insulin-like growth factors (IGFs) in the circulation. IGFBP-3 antagonizes the growth-promoting and anti-apoptotic activities of IGFs in experimental systems, but in certain contexts can increase IGF bioactivity, probably by increasing its half-life. The goal of this study was to investigate the role of IGFBP-3 in breast carcinogenesis and breast cancer metastasis.

Characterization of a novel founder MSH6 mutation causing Lynch syndrome in the French Canadian population.

We identified an MSH6 mutation (c.10C>T, p.Gln4*) causing Lynch syndrome (LS) in 11 French Canadian (FC) families from the Canadian province of Quebec.

Mutation analysis of PALB2 in BRCA1 and BRCA2-negative breast and/or ovarian cancer families from Eastern Ontario, Canada.

Background: PALB2 has emerged as a breast cancer susceptibility gene. Mutations in PALB2 have been identified in almost all breast cancer populations studied to date, but the rarity of these mutations and lack of information regarding their penetrance makes genetic counseling for these families challenging. We studied BRCA1/2 -negative breast and/or ovarian cancer families to a) assess the contribution of PALB2 mutations in this series and b) identify clinical, pathological and family history characteristics that might make PALB2 screening more efficient.

RSF1 and not cyclin D1 gene amplification may predict lack of benefit from adjuvant tamoxifen in high-risk pre-menopausal women in the MA.12 randomized clinical trial.

Most women with estrogen receptor expressing breast cancers receiving anti-estrogens such as tamoxifen may not need or benefit from them. Besides the estrogen receptor, there are no predictive biomarkers to help select breast cancer patients for tamoxifen treatment. CCND1 (cyclin D1) gene amplification is a putative candidate tamoxifen predictive biomarker.

Endoplasmic reticulum stress induces PRNP prion protein gene expression in breast cancer.

Introduction: High prion protein (PrP) levels are associated with breast, colon and gastric cancer resistance to treatment and with a poor prognosis for the patients. However, little is known about the underlying molecular mechanism(s) regulating human PrP gene (PRNP) expression in cancers. Because endoplasmic reticulum (ER) stress is associated with solid tumors, we investigated a possible regulation of PRNP gene expression by ER stress.

An integrated genomic approach identifies ARID1A as a candidate tumor-suppressor gene in breast cancer.

Tumor-suppressor genes (TSGs) have been classically defined as genes whose loss of function in tumor cells contributes to the formation and/or maintenance of the tumor phenotype. TSGs containing nonsense mutations may not be expressed because of nonsense-mediated RNA decay (NMD). We combined inhibition of the NMD process, which clears transcripts that contain nonsense mutations, with the application of high-density single-nucleotide polymorphism arrays analysis to discriminate allelic content in order to identify candidate TSGs in five breast cancer cell lines.

[Juvenile xanthogranuloma of the nasal cavity].

JXG is a benign lesion of unknown incidence. It is the most frequent type of non-langerhans histiocytosis with a median age of 2 years. It usually presents as isolated cutaneous lesions.