Germline Mutation of the LKB1/STK11 Gene with Loss of the Normal Allele in an Aggressive Breast Cancer of Peutz-Jeghers Syndrome

Oncology ◽  
2004 ◽  
Vol 67 (5-6) ◽  
pp. 476-479 ◽  
Author(s):  
Chikashi Nakanishi ◽  
Tatsuro Yamaguchi ◽  
Takeru Iijima ◽  
Shigehira Saji ◽  
Masakazu Toi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Germline Mutation ◽  
Normal Allele ◽  
Stk11 Gene ◽  
Peutz Jeghers Syndrome ◽  
Aggressive Breast Cancer

scholarly journals STK11 gene mutations among patients with sporadic breast cancer

Genetika ◽  
2017 ◽  
Vol 49 (2) ◽  
pp. 399-413
Author(s):  
Georgi Antov ◽  
Maria Krasteva ◽  
Silvia Andonova ◽  
Alexey Savov ◽  
Svetla Angelova ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Sporadic Breast Cancer ◽  
Rare Event ◽  
Gene Mutations ◽  
Genetic Alterations ◽  
Minor Role ◽  
Stk11 Gene ◽  
Blood Specimens ◽  
Peutz Jeghers Syndrome ◽  
A Minor

Germline mutations affecting STK11 (LRG_319) are profoundly studied in relation to Peutz-Jeghers syndrome, predisposing to the development of various cancers at multiple sites. Though somatic mutations in STK11 are found to be present in several cancers, limited data on its involvement in sporadic breast cancer are available. The present study aims to evaluate the frequency and spectrum of genetic alterations in STK11 in a group of Bulgarian patients with sporadic breast cancer. A total of 73 tumor and 22 corresponding blood specimens derived from the patients, and 10 blood samples from clinically healthy controls were analyzed. High Resolution Melting analysis followed by Sanger sequencing and bioinformatic prediction tools were utilized. Seven patients (9.58%) harbored STK11 alterations, only two (2.74%) of which are exonic: one nonsense c.322A>T; p.K108X (deleterious) and one missense c.440G>A; p.Arg147His (of unknown significance). Two intronic variants were also observed: c.290+36G>T and c. *16+18C>A (novel). To our knowledge the results represent the first data indicating presence of STK11 alterations in patients with sporadic breast cancer. The limited number of the detected deleterious mutations indicates that mutational inactivation of the gene is a rare event and probably plays a minor role in sporadic breast carcinogenesis.

A Case of Peutz-Jeghers Syndrome With Breast Cancer, Bilateral Sex Cord Tumor With Annular Tubules, and Adenoma Malignum Caused by STK11 Gene Mutation

2009 ◽  
Vol 19 (9) ◽  
pp. 1591-1594 ◽  
Author(s):  
Aine Clements ◽  
Katina Robison ◽  
Cornelius Granai ◽  
Margaret M. Steinhoff ◽  
Jennifer Scalia-Wilbur ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Autosomal Dominant ◽  
Pelvic Mass ◽  
Gynecologic Malignancies ◽  
Autosomal Dominant Disorder ◽  
Stk11 Gene ◽  
Stromal Tumors ◽  
Increased Risk ◽  
Adenoma Malignum ◽  
Peutz Jeghers Syndrome

Background:Peutz-Jeghers syndrome (PJS) is a rare autosomal dominant disorder, and women with this syndrome are at an increased risk of developing intestinal and extraintestinal malignancies including breast and gynecologic malignancies. This case report presents a patient with PJS with a concomitant breast cancer, bilateral stromal tumors with annular tubules of the ovaries, and adenoma malignum of the cervix.Case:A 43-year-old woman presented with an advanced-stage breast cancer and a pelvic mass. The patient was treated with neoadjuvant chemotherapy followed by laparotomy with a hysterectomy and oophorectomy. Final pathologic examination revealed a concomitant breast cancer with metastasis to the ovaries, bilateral stromal tumors with annular tubules of the ovaries, and adenoma malignum of the cervix.Conclusions:Patients with PJS are at a high risk for intestinal and extraintestinal malignancies and can present with multiple concomitant malignancies.

scholarly journals A novel germline mutation (c.A527G) in STK11 gene causes Peutz–Jeghers syndrome in a Chinese girl

Medicine ◽  
2017 ◽  
Vol 96 (49) ◽  
pp. e8591 ◽  
Author(s):  
Zi-Ye Zhao ◽  
Yu-Liang Jiang ◽  
Bai-Rong Li ◽  
Fu Yang ◽  
Jing Li ◽  
...  
Keyword(s):  
Germline Mutation ◽  
Stk11 Gene ◽  
Chinese Girl ◽  
Peutz Jeghers Syndrome

scholarly journals Cytocompatibility of stabilized black phosphorus nanosheets tailored by directly conjugated polymeric micelles for human breast cancer therapy

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
M. Biedulska ◽  
P. Jakóbczyk ◽  
M. Sosnowska ◽  
B. Dec ◽  
A. Muchlińska ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Polymeric Micelles ◽  
Black Phosphorus ◽  
Environmental Stability ◽  
Breast Cancer Cell Lines ◽  
The Novel ◽  
Ft Ir ◽  
Dose Dependent ◽  
Aggressive Breast Cancer

AbstractThe novel procedure of few-layer black phosphorus (FLBP) stabilization and functionalisation was here proposed. The cationic polymer PLL and non-ionic PEG have been involved into encapsulation of FLBP to allow sufficient time for further nanofabrication process and overcome environmental degradation. Two different spacer chemistry was designed to bind polymers to tumor-homing peptides. The efficiency of functionalisation was examined by RP-HPLC, microscopic (TEM and SEM) and spectroscopic (FT-IR and Raman) techniques as well supported by ab-initio modelling. The cell and dose dependent cytotoxicity of FLBP and its bioconjugates was evaluated against HB2, MCF-7 and MDA-MB-231 cell lines. Functionalisation allowed not only for improvement of environmental stability, but also enhances therapeutic effect by abolished the cytotoxicity of FLBP against HB2 cell line. Moreover, modification of FLBP with PLL caused increase of selectivity against highly aggressive breast cancer cell lines. Results indicate the future prospect application of black phosphorus nanosheets as nanocarrier, considering its unique features synergistically with conjugated polymeric micelles.

scholarly journals Identification of a small molecule as inducer of ferroptosis and apoptosis through ubiquitination of GPX4 in triple negative breast cancer cells

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Yahui Ding ◽  
Xiaoping Chen ◽  
Can Liu ◽  
Weizhi Ge ◽  
Qin Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Death ◽  
Small Molecule ◽  
Mode Of Action ◽  
Rna Silencing ◽  
Breast Cancer Cells ◽  
Triple Negative ◽  
Parent Compound ◽  
Aggressive Breast Cancer

Abstract Background TNBC is the most aggressive breast cancer with higher recurrence and mortality rate than other types of breast cancer. There is an urgent need for identification of therapeutic agents with unique mode of action for overcoming current challenges in TNBC treatment. Methods Different inhibitors were used to study the cell death manner of DMOCPTL. RNA silencing was used to evaluate the functions of GPX4 in ferroptosis and apoptosis of TNBC cells and functions of EGR1 in apoptosis. Immunohistochemical assay of tissue microarray were used for investigating correlation of GPX4 and EGR1 with TNBC. Computer-aided docking and small molecule probe were used for study the binding of DMOCPTL with GPX4. Results DMOCPTL, a derivative of natural product parthenolide, exhibited about 15-fold improvement comparing to that of the parent compound PTL for TNBC cells. The cell death manner assay showed that the anti-TNBC effect of DMOCPTL mainly by inducing ferroptosis and apoptosis through ubiquitination of GPX4. The probe of DMOCPTL assay indicated that DMOCPTL induced GPX4 ubiquitination by directly binding to GPX4 protein. To the best of our knowledge, this is the first report of inducing ferroptosis through ubiquitination of GPX4. Moreover, the mechanism of GPX4 regulation of apoptosis is still obscure. Here, we firstly reveal that GPX4 regulated mitochondria-mediated apoptosis through regulation of EGR1 in TNBC cells. Compound 13, the prodrug of DMOCPTL, effectively inhibited the growth of breast tumor and prolonged the lifespan of mice in vivo, and no obvious toxicity was observed. Conclusions These findings firstly revealed novel manner to induce ferroptosis through ubiquitination of GPX4 and provided mechanism for GPX4 inducing mitochondria-mediated apoptosis through up-regulation of EGR1 in TNBC cells. Moreover, compound 13 deserves further studies as a lead compound with novel mode of action for ultimate discovery of effective anti-TNBC drug.

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