TP53 deletion

This study highlights how Trp53 deletion promotes the perfect storm of inflammation and stemness, driving colon cancer progression. Trp53 deletion dramatically shortened AOM/DSS latency and improved tumor induction efficiency, offering an excellent inflammation-driven CRC model.

Sequencing of the two lymphomas demonstrated clonal relatedness of the two processes. To our knowledge, this is the first report of a splenic marginal zone lymphoma with a TP53 deletion at diagnosis, evolving into a large B-cell lymphoma with a CCND1 rearrangement.

This combination induced replicative stress and caspase-mediated cell death and was highly effective in resistant/refractory patient samples with TP53 deletion and/or mutation and in TP53 -/- NCI-H929 xenografted NOD-scid IL2Rgamma mice. Our in vitro, ex vivo, and in vivo data provide the rationale for combined CTPS1 and ATR inhibition for the treatment of p53-deficient patients.

The majority of ZsGreen conjugated with minOVA was observed in the conventional type 2 DCs (cDC2), whereas cDC1 has minimal. These data indicate that tumor immunogenicity regulates host immune responses, and tumor neoantigen is mostly recognized by cDC2 cells, which may play a critical role in initiating antitumor immune responses in an orthotopic murine lung cancer model.

An endoscopic approach is popular for tissue biopsy. Bone marrow biopsy with a smear, serum or urine protein electrophoresis, and immunofixation electrophoresis are crucial upon the appearance of target organ damage.

Importantly, the combination of OPN-51107 and venetoclax exhibited synergistic cytotoxicity in ibrutinib-resistant CLL cells and patient-derived CLL samples regardless of R/R or deletion status. This study establishes the preclinical efficacy of using OPN-51107 and venetoclax in combination in therapy-resistant and/or high-risk CLL, lending support for its further development as a combination therapy.

In conclusion, 17p13 deletions were most commonly seen in p53 negative cancers, supporting their role as a cause for the p53 null phenotype in urothelial cancer. The association of 17p13 deletions with high grade and advanced pT stage may reflect increasing genomic instability going along with stage and grade progression.

P2, N=235, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025

The UHR model, which integrates the presence of +1q21 with no-ASCT and TP53 deletion, is designed to identify the early relapse subgroup among patients with +1q21 in NDMM.

Time limited AO was well tolerated and resulted in deep remissions allowing for time limited BTKi tx. 40% ofpts achieved U-MRD with 13C of tx, 86% of these patients maintained U-MRD 3 cycles post completion of tx. This study is fully accrued.

Nine tumors were tested with Nanocind CINSARC® signature and all were classified in low risk of recurrence. We propose, based on our observations, a diagnostic approach of these challenging lesions.

Consequently, our GBM models have proven to be invaluable resources for identifying early disease biomarkers in glioblastoma, as they closely mimic the human disease. The insights gained from these models may pave the way for potential advancements in the diagnosis and treatment of this challenging brain tumor.

A highly efficient and liver-specific BAC-Alb-FlpO mouse model was developed. In combination with other Cre lines, different genes can be manipulated sequentially in the same cell, or distinct genetic changes can be induced in different cell types of the same organism.

TP53mut retained its significance even in the presence of any Revised International Staging System (HR 2.1; 95% CI 1.1-3.8; p=0.015) for OS. The detection of additional cases with TP53 aberrations, as well as poor survival associated with the presence of mutation alone, supports TP53mut testing in NDMM at least in patients without TP53del and other high-risk cytogenetic abnormalities.

Noteworthily, neither carboplatin and oxaliplatin resistance nor p53 deletion impacted on their anticancer efficacy. In contrast, dppe silver drugs induced paraptosis, a novel recently described form of programmed cell death. Together with the good tumor specificity of this compound's class, this work suggests that dppe-containing silver complexes could be interesting drug candidates for the treatment of resistant ovarian cancer.

Higher CHK2 expression was associated with poorer treatment responses and disease outcomes. Higher CHK2 expression and positive p53 together with a TP53 deletion could be a prognostic marker of unfavorable disease outcomes in patients with germline truncating mutations in CHEK2.

FISH analysis of FFPE PT-NHLs detects genetic abnormalities, even in small specimens, in approximately 60% of cases. While BCL2 and BCL6 abnormalities are infrequent, MYC and 11q abnormalities were seen in 1/3 of tested cases. Interestingly, the classic 11q aberration was seen only in GC-DLBCLs (all patients alive), while extra copies were seen in non-GC cases (all patients with follow-up have died), including 2 EBV positive, suggesting different pathogenetic pathways with unique biologic behavior.

Strong p53 by IHC in more than 30% of neoplastic cells is a useful tool to screen TP53 mutations. In our series, aLBCL did not have significant concurrent alterations between p53 and MYC pathways.

P1/2, N=72, Recruiting, M.D. Anderson Cancer Center | Active, not recruiting --> Recruiting

TP53 and RAD51D co-deleted organoids exhibited heightened sensitivity to platinum, poly-ADP ribose polymerase inhibitors (PARPi), and cell cycle-related medication. In summary, our research highlighted the use of FTE organoids with RAD51D mutations as an invaluable in vitro platform for the early detection of carcinogenesis, mechanistic exploration, and drug screening.

Multivariate analysis suggested that 1q21+ , EMD-S, elevated lactate dehydrogenase (LDH) levels, and P53 deletion were independent risk factors for poor prognosis in patients with EMD. In patients with 1q21+ EMD, hypercalcemia, elevated LDH levels, and P53 deletion were independent adverse risk prognostic factors.

Notably, the development of allograft models and precancerous precursor models from SCLC GEMMs provides complementary approaches to GEMMs to study tumor cell-immune microenvironment interactions and test new therapeutic strategies to enhance response to immunotherapy. Ultimately, the new generation of SCLC models can accelerate research and help develop new therapeutic strategies for SCLC.

P2, N=235, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting | N=440 --> 235

IL30 regulates the crosstalk between PC and EC and reshapes their transcriptional profiles, triggering angiogenic, immunoregulatory and oncogenic gene expression programs. These findings highlight the angiostatic and oncostatic efficacy of targeting IL30 to fight PC.

A karyotype on bone marrow remains mandatory at diagnosis of MDS with complementary molecular analyses now required. Analyses with FISH or other technologies providing similar information can be necessary to complete and help in case of karyotype failure, for doubtful CA, for clonality assessment, and for detection of TP53 deletion to assess TP53 biallelic alterations.

p53R245W GOF properties increased carcinoma initiation, fueled mixed hepatocholangial carcinoma incidence, and tripled metastatic disease. Collectively, our in vivo studies indicate that p53R245W has stronger tumor promoting activities than Trp53 loss in the context of NASH.

Additionally, inhibition of PRL2 with a small molecule inhibitor phenocopies the effect of genetic deletion of Prl2 and reduces Tp53 deficiency-induced tumor growth. Taken together, the results further establish PRL2 as a negative regulator of PTEN and highlight the potential of PRL2 inhibition for PTEN augmentation therapy in cancers with wild-type PTEN expression.

With static and dynamic assessment, we can identify a group of UHR-MM with survival no more than 3 years as early as possible. For these patients, we need more potent therapy model to improve their survival.

Our study demonstrates an objective assessment of BCL2 and MCL1 expression by FCM. BCL2 PC/T,MCL1 PC/T and BCL2 PC /MCL1 PC were significantly higher in myeloma cells compared to non-clonal PCs. Low MCL1 expression or high BCL2/MCL1 ratio was associated with IGH: : CCND1; while strong MCL1 and low BCL2/MCL1 ratio was most frequent in 1q21 amplification.

Taken together, our findings emphasized that 1q21+ increased the possibility of disease progression and predicted poor survival in EMD patients. 1q21+ EMD tends to be associated with other high risk disease factors. ASCT may not overcome the adverse effect of 1q21+ in EMD patients.

Patients undergo conditioning (melphalan alone or plus fludarabine) followed by ASCT on Day 0 and trovo-cel 3...5%) had received daratumumab, with six having been treated with dara-based quadruplet or quintuplet therapy as a front setting...6%) received tocilizumab and glucocorticoid for CRS... The preliminary results of this clinical trial show a promising safety and efficacy profile of trovo-cel followed ASCT in UHR-MM patients. Although the follow-up time is relatively limited, we are looking forward to a consistently good safety and efficacy outcome in long-term follow-up and in more patients recruited later.

29 patients received azacitidine-based treatment and 42 patients received decitabine-based treatment, the median OS were 5. TP53 gene abnormalities in patients with MDS are frequently accompanied by complex karyotypes and abnormalities in chromosomes 5, 7, 8, and 20. Currently, the prognosis of MDS patients with TP53 gene abnormalities remains poor, and treatment regimens based on demethylating agents have limited efficacy in this population. In combination with venetoclax or Allo-HSCT also can not improve survival.

Evidence supporting the use of intravenous methotrexate (MTX) or arabinoside (AraC) in high-risk patients is growing, however, the use of other agents remains to be defined...All patients are need to receive IT thiotepa 10 mg and dexamethasone 5 mg on day 1 of each cycle of chemotherapy for at least 4 cycles...6%) patients received rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (RCHOP), 5 (18...1%) patients received BTK inhibitor, lenalidomide with rituximab (ZR2) followed by RCHOP, and 4 (14...ConclusionProphylactic intrathecal thiotepa is an effective and side-effects manageable measure for preventing secondary central nervous system involvement in high-risk DLBCL. Longer follow-up and larger-scale prospective trial is needed to testify this measure.

Two patients had deletion of SMARCA4 at diagnosis, that confers resistance to the BCL-2 inhibitor venetoclax (Agarwal et al...Mutations in the NF-κB alternative pathway, responsible for resistance to ibrutinib, are found in both LR and HR patients. ConclusionIn this small cohort of MCL patients included in a trial, complex structural alterations were identified by OGM at the time of diagnosis. OGM is a very promising technology that demonstrated its potential in the cytogenetic prognostic staging of MCL.

The GFCH present here the overview of genomics alterations identified in MM and related PCs diseases associated with their prognostic factor, when available, and recommendations from an expert group for identification and characterization of those alterations. This work is the update of previous 2016 recommendations.

The recent study has shown that the loss of p53 leads to excessive cholesterol ester biosynthesis, which promotes hepatocellular carcinoma in mice. Blocking cholesterol esterification improves treatment outcomes, particularly for liver cancers with p53 deletions/mutations that originate in a background of non-alcoholic fatty liver disease.

By identifying specific gene mutations and differences in genetic markers, the study provided insights for the development of targeted diagnostic methods and personalised treatment strategies, ultimately improving the clinical outcomes in the field of oncology.

A Kaplan-Meier analysis of median overall survival (mOS) in patients with AML and MDS with RC at diagnosis revealed that patients who received supportive care had significantly shorter mOS than patients who received hypomethylating agents (HMA), HMA/Venetoclax(VEN), or anthracycline-based chemotherapy (log rank test, p = 0.001)...Comparing response to type of therapy and outcomes of patients, we conclude that the mOS in patients with RC without therapy is significantly shortened compared with any of the therapeutic options described above, and that the addition of VEN to HMA did not positively influence mOS or PFS compared to HMA alone or chemotherapy in our cohort. Furthermore, the presence of a complex karyotype or a mutation and/or deletion of TP53 with a RC was not independently associated with inferior mOS, suggesting that the presence of a ring chromosome alone may be an important adverse risk factor in myeloid malignancies.

Unexpectedly, PTEN deletions are associated with poor survival in MSS CRC, whereas PTEN mutations are associated with improved survival in MSI CRC. These and other data suggest use of PTEN as a prognostic marker is valid in CRC, but such use must consider driver mutation landscape, tumor subtype, and category of PTEN alteration.