Stk11

UNLABELLED: Never-smoker lung adenocarcinoma (NSLA) is prevalent in Asian populations, particularly in women. EGFR mutations and anaplastic lymphoma kinase (ALK) fusions are major genetic alterations observed in NSLA, and NSLA with these alterations have been well studied and can be treated with targeted therapies. To provide insights into the molecular profile of NSLA without EGFR and ALK alterations (NENA), we selected 141 NSLA tissues and performed proteogenomic characterization, including whole genome sequencing (WGS), transcriptomic, methylation EPIC array, total proteomic, and phosphoproteomic analyses...

Lung cancer is a paradigm for a genetically driven tumor. A variety of drugs were developed targeting specific biomarkers requiring testing for tumor genetic alterations in relevant biomarkers. Different next-generation sequencing technologies are available for library generation: 1) anchored multiplex-, 2) amplicon based- and 3) hybrid capture-based-PCR. Anchored multiplex PCR-based sequencing was investigated for routine molecular testing within the national Network Genomic Medicine Lung Cancer (nNGM). Four centers applied the anchored multiplex ArcherDX-Variantplex nNGMv2 panel to re-analyze samples pre-tested during routine diagnostics...

Metabolism reprogramming within the tumor microenvironment (TME) can have a profound impact on immune cells. Identifying the association between metabolic phenotypes and immune cells in lung adenocarcinoma (LUAD) may reveal mechanisms of resistance to immune checkpoint inhibitors (ICIs). Metabolic phenotypes were classified by expression of metabolic genes. Somatic mutations and transcriptomic features were compared across the different metabolic phenotypes. The metabolic phenotype of LUAD is predominantly determined by reductase-oxidative activity and is divided into two categories: redoxhigh LUAD and redoxlow LUAD...

In this phase 2 multicenter study, we evaluated the efficacy and safety of lifileucel (LN-145), an autologous tumor-infiltrating lymphocyte cell therapy, in patients with metastatic non-small cell lung cancer (mNSCLC) who had received prior immunotherapy and progressed on their most recent therapy. The median number of prior systemic therapies was 2 (range, 1-6). Lifileucel was successfully manufactured using tumor tissue from different anatomic sites, predominantly lung. The objective response rate was 21...

Everolimus is widely used in patients with advanced ER-positive, HER2-negative breast cancer. We looked at alterations in the PIK3CA/AKT/mTOR pathway in a multicenter cohort as potential biomarkers of efficacy. Patients with advanced ER-positive, HER2-negative breast cancer treated with everolimus and endocrine therapy between 2012 and 2014 in two cancer centers were included. Targeted sequencing examined mutations in PIK3CA, ESR1, and AKT1 genes. An immunochemical analysis was conducted to evaluate expression of PTEN, INPP4B, STK11, p4EBP1, and pS6...

[This retracts the article DOI: 10.1155/2022/8636527.].

Patient-derived organoids (PDOs) retain the original tumor's characteristics to a large degree and allow direct evaluation of the drug sensitivity, thereby emerging as a valuable resource for both basic and preclinical researches. Whereas most past studies stereotypically adopted a single PDO as an avatar of the patient, it remains to be investigated whether this assumption can be justified even for the tumor with spatial diversity. To address this issue, we established and characterized multiple PDOs originating from various sites of a patient with advanced uterine carcinosarcoma (UCS)...

BACKGROUND: Stools from colorectal cancer patients are noninvasive samples that could be used to compare the frequency of hotspot mutations between two different ethnic cohorts. MATERIALS AND METHODS: We collected stool samples from the Iranian cohort (52 patients and 49 controls) and the Finnish cohort (40 patients and 14 controls). Following stool DNA extraction, we used the AmpliSeq Colon and Lung Cancer panel to prepare DNA libraries before sequencing. RESULTS: The Iranian cohort exhibited 35 hotspot mutations in the BRAF , ERBB4 , FBXW7 , FGFR1 , FGFR3 , KRAS , MAP2K , MET , NRAS , PIK3C , SMAD4 , and TP53 genes...

Although lung cancer remains the most common cause of global cancer-related mortality, the identification of oncogenic driver alterations and the development of targeted drugs has dramatically altered the therapeutic landscape. In this retrospective study, we found that 97.7% samples carried at least one mutation in the 25 genes tested in our cohort. 53.6% samples were positive for EGFR mutations, followed by TP53 (41.1%), KRAS (11.8%), ERBB2 (4.3%). EGFR mutations were mainly found in female adenocarcinomas, while TP53 was mainly found in male non-adenocarcinomas...

A 28-year-old female with a history of treatment for small intestinal polyps and characteristic pigmentation of her lip was clinically diagnosed with Peutz-Jeghers syndrome(PJS). Her sister had the pathogenic variant of STK11 upon genetic testing. A 20-mm polyp was identified in the second part the patient's duodenum on routine gastrointestinal surveillance, and biopsy revealed a well-differentiated adenocarcinoma. Laparoscopic partial duodenectomy with endoscopy was planned. After confirming the location of the tumor and Kocherization using a laparoscope, the polyp was resected via submucosal dissection under direct visualization with a small incision...

Peutz-Jeghers syndrome is a rare, autosomal dominant polyposis syndrome. Presenting with a remarkable phenotype including development of characteristic gastrointestinal polyps, mucocutaneous pigmentations, and an increased risk of cancer, the syndrome has been subject to many studies concerning the natural course of disease. In most patients, pathogenic germline variants are detected in the STK11 gene including cases of mosaicism and structural variants. Yet, studies assessing the effect of surveillance, understanding of cancer development, as well as clinical studies evaluating chemoprevention are lacking...

The molecular mechanisms underpinning the development of metachronous tumors in the remnant bile duct following surgical resection of primary biliary tract carcinomas (BTCs) are unknown. This study aimed to elucidate these mechanisms by evaluating the clinicopathologic features of BTCs, the alterations to 31 BTC-related genes on targeted sequencing, and the aberrant expression of p53, p16, SMAD4, ARID1A and β-catenin on immunohistochemistry. Twelve consecutive patients who underwent resection of metachronous BTCs following primary BTC resection with negative bile duct margins were enrolled...

We performed the next-generation sequencing (NGS) analysis of a rare grade 1 brain meningioma (angiomatous type) and a common grade 1 spinal meningioma (psammomatous type) and compared their mutation profiling. The data were analysed using the Ion Reporter 5.16 programme (Thermo Fisher Scientific, Waltham, MA). Sequencing analysis identified 10 novel variants and two previously reported variants that were common between these two tumours. Nine variants were missense, which included an insertion in EGFR c.1819_1820insCA, causing frameshifting, and a single nucleotide deletion in HRAS and HNF1A genes, causing frameshifting in these genes...

Docetaxel +/- ramucirumab remains the standard-of-care therapy for patients with metastatic non-small-cell lung cancer (NSCLC) after progression on platinum doublets and immune checkpoint inhibitors (ICIs). The aim of our study was to investigate whether the cancer gene mutation status was associated with clinical benefits from docetaxel +/- ramucirumab. We also investigated whether platinum/taxane-based regimens offered a better clinical benefit in this patient population. A total of 454 patients were analyzed (docetaxel +/- ramucirumab n=381; platinum/taxane-based regimens n=73)...

Pancreatic cancer is a malignant tumor of the digestive system. It is highly aggressive, easily metastasizes, and extremely difficult to treat. This study aimed to analyze the genes that might regulate pancreatic cancer migration to provide an essential basis for the prognostic assessment of pancreatic cancer and individualized treatment. A CRISPR knockout library directed against 915 murine genes was transfected into TB 32047 cell line to screen which gene loss promoted cell migration. Next-generation sequencing and PinAPL...

Metastatic prostate cancer (PCa) poses a significant therapeutic challenge with high mortality rates. Utilizing CRISPR-Cas9 in vivo, we target five potential tumor suppressor genes (Pten, Trp53, Rb1, Stk11, and RnaseL) in the mouse prostate, reaching humane endpoint after eight weeks without metastasis. By further depleting three epigenetic factors (Kmt2c, Kmt2d, and Zbtb16), lung metastases are present in all mice. While whole genome sequencing reveals few mutations in coding sequence, RNA sequencing shows significant dysregulation, especially in a conserved genomic region at chr5qE1 regulated by KMT2C...

BACKGROUND: In light of the ongoing clinical development of KRAS G12D-specific inhibitors, we sought to investigate the clinicopathologic, co-occurring genomic features and outcomes of patients with KRAS G12D-mutant lung adenocarcinoma. METHODS: 3828 patients with completely resected primary lung adenocarcinomas were examined for KRAS mutations between 2008 and 2020. The association between KRAS G12D and clinicopathologic features, molecular profiles, and outcomes was investigated...

INTRODUCTION: In patients with advanced NSCLC (aNSCLC), the impact of KRAS mutations (m) and comutations with STK11 and KEAP1 on outcomes across different PD-L1 levels remains incompletely understood. We aimed to investigate the frequency of KRAS mutations and comutations across PD-L1 levels, and the association between these mutations and survival, stratified by PD-L1 expression. METHODS: We conducted a nationwide cohort study of patients diagnosed with aNSCLC between 2016 and 2021 treated with frontline (chemo)immunotherapy, who underwent molecular genotyping including KRAS, STK11, and KEAP1...

BACKGROUND: STK11/LKB1 mutations have been associated with primary resistance to PD-1 axis inhibitors and poor prognosis in advanced KRAS-mutant lung adenocarcinoma. This study aimed to assess the prognostic significance of STK11/LKB1 alterations in localized non-squamous non-small cell lung carcinoma (non-sq NSCLC). PATIENTS AND METHODS: Surgical samples from patients undergoing complete resection for stage IIa, IIb, or IIIa (N2 excluded) non-sq NSCLC in the randomized adjuvant phase II trial (NCT00775385 IFCT-1801 TASTE trial) were examined...

BACKGROUND: Programmed cell death ligand 1 (PD-L1) blocking therapy has transformed the treatment of lung adenocarcinoma (LUAD), which has significantly changed the landscape of immunotherapy. We aimed to explore specific cell subpopulations to understand tumor progression and identify markers of response to PD-L1 blocking therapy. METHODS: Bulk, fluorescence-activated cell sorting (FACS), and single-cell RNA (scRNA) sequencing were used to profile CXCL13 , EPSTI1 , and CDK1 ...