FANCI mutation

P2, N=12, Completed, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Active, not recruiting --> Completed | N=30 --> 12

They received postoperative treatment and were monitored for 20 and 26 months, showing good recovery. The phenotypic and genotypic spectrum of AS in pediatric population was expanded by these two patients, which requires the accumulating more cases to gain a deeper understanding.

This study revealed a significantly higher MSI-H distribution rate in early-onset colorectal cancer, and EOCRC exhibits a distinct mutational signature coupled with higher PD-L1 expression. These findings hold promise in guiding personalized therapeutic strategies for improved disease management in EOCRC patients.

P2, N=30, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Recruiting --> Active, not recruiting

P2, N=30, Recruiting, West Cancer Center | Not yet recruiting --> Recruiting

Mutations involving NF1, SUZ12, or EED were absent in all tested specimens. In conclusion, H3K27me3 expression may be lost in as many as 8% of sarcomatoid carcinomas which can pose as a potential diagnostic pitfall, especially in challenging sarcomatoid carcinoma specimens with absent keratin staining.

HER2-low BC patients have distinct germline mutational signatures and differential clinical outcomes under neoadjuvant systemic therapy. These results have provided additional evidence that HER2-low patients comprise a fourth subtype of BC that needs to be accounted for separately in terms of clinical treatment and outcome reporting.

In summary, comprehensive study of the clinical and genetic features of patients with multiple primary malignancies may improve diagnosis and treatment in the future. Mutations in FANC genes might be a predisposition to tumorigenesis of lymphoma patients with a second solid malignancy.

We generated an iPSC line (YBLi006-A) from peripheral blood mononuclear cells (PBMCs) of a patient carrying a mutation in FANCIgene (NM_001376911.1, NM_001376910.1, NM_001113378.2; c.80G > T, c.257C > T, c.2225G > C; p.Gly27Val, p.Ala86Val, p.Cys742Ser) using non-integrating Sendai virus technology. This unique breast cancer patient-derived-iPSC line will be resourceful to analyze the entire coding sequence and splicing sites ofFANCIin high-risk familial breast cancer.

To our knowledge, this is the first report of pathogenic germline mutations in the FANCI and FANCM genes and heterozygous germline missense mutation in exon 5 of the FH gene c.563A>T:p.N188I in RCC. Young RCC patients, patients with bilateral or multifocal RCC, or patients with nccRCC are more likely to have pathogenic/potentially pathogenic germline mutations.

Lastly, according to preliminary in silico results, the co-occurrence of site-specific hypermethylation in MSH2 and PALB2 is possibly due to the absence of interaction of the common transcription factor SP4 in a GC-box site. These findings expand our vision of the genetic and epigenetic mechanisms of susceptibility to this disease.

P2, N=30, Recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: May 2023 --> May 2024 | Trial primary completion date: Dec 2022 --> Dec 2023

Our study investigated the clinical features and genotype/phenotype correlation of 148 Chinese pediatric FA patients, providing new insight into FA.

The parental consanguinity among patients was 51%.The most frequent anomaly was short stature (45 patients, 65%), skin changes (11, 15%), urogenital abnormalities (21, 30%), dysmorphism/craniofacial abnormalities (25, 36%); A significant minority of patients (29%) had no other physical anomaly and presented with bone marrow failure or hematological malignancy.Diagnostic Tests: 68 patients (70%) had a positive CB analysis with diepoxybutane (DEB) or mitomycin-C (MMC) testing; in 5 patients (5%) DEB testing was borderline and 1 (1%) had a normal CBA but had a diagnostic phenotype/- family history and presence of a homozygous mutation in a known FA related gene...We report long term outcomes of a large cohort of AYA patients with FA in Saudi Arabia.FANCA is the most frequent gene affected.FA patients have a significant risk of malignancies that reduces survival. Early detection and screening of malignancies is crucial. Further progress is required in improving outcomes in transplanted patients with reduced toxicity and less genotoxic therapies , including gene therapy.

It partially explained the reason for the co-occurrence of SBL and HB. Taken together, we provided valuable resources for deciphering cellular heterogeneity and adaptive change of tumor cells after chemotherapy for synchronous SBL and HB, providing insights into the mechanisms leading to synchronous pediatric tumors.

P2, N=30, Recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Nov 2022 --> May 2023 | Trial primary completion date: May 2022 --> Dec 2022

This study analyzed clinical and mutational characteristics of reversion mutations in HRR genes, which could occur as single or multiple variants to restore the function of predisposed pathogenic HRR mutations, resulting in resistance to platinum-based chemotherapies or PARP inhibitors. Monitoring these mutations with tissue or liquid biopsy samples are crucial for treatment guidance.

Non-BRCA HRR mutations also account for a very important proportion and might be associated with poor prognosis in HGSOC. It is suggested that HRR gene mutations need to be detected in EOC tissues and germline status be further clarified in clinical algorithm for potential targeted therapy, genetic screening, and prognosis prediction.

We identified CHEK2 as a regulator of DNA damage response and perhaps as a gene involved in CRC germline predisposition. These findings link CRC predisposition to the DNA repair pathway, supporting the connection between genome integrity and cancer risk.

Somatic variants characteristics may distinguish ccpRCC from ccRCC or pRCC and germline VAFAs may be a molecular characterization of ccpRCC. Compared with ccRCC or pRCC, ccpRCC patients may be significantly correlated with higher risk of developing second primary malignancy.

P2, N=30, Not yet recruiting, West Cancer Center

Our results show distinct differences in genomic profile between the primary tumor and the brain metastasis. Identifying the mutation signatures of brain metastases is therefore necessary for selecting targeted therapy, and this change in clinical management may radically improve the prognosis.

P2, N=30, Recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Nov 2021 --> Nov 2022 | Trial primary completion date: May 2021 --> May 2022

Here we provide the first evidence of the molecular etiology of a rare HMEC associated with germline Fanconi's anemia gene mutations and somatic GNAS R201H mutation.

This is strongly supported by transcriptome findings on CD161’s distinct T cell-B cell activation signatures with elevated VCAM1, GPR18 and PTPRC.Furthermore, we determined in HPV(-)HNSCC, 12 gene mutations (CYLD, CCDC172, SAMD7, CDKL1, WDR47, MFSD9, PWWP2B, UXT, GP6, FAM9A, ARSE, UGCG) are associated with elevated CD161, while in HPV(+)HNSCC, 9 gene mutations (COL6A2, ZHX, SCN3A, GNA15, CDH3, SAMD7, MTUS1, FANCI, ARSE) are linked to elevated CD161. Our data first identified CD161 as a single prognostic biomarker gene with potential clinical utility, discovering its strong ties to high CD8+T cell, B cell and activated NK cell in HNSCC.

In CaP cell lines, LP184 turned out equipotent as standard chemotherapeutic Docetaxel, 100-2000 times more potent than another alkylating agent Cisplatin, and 100-9000 times more potent than PARP inhibitor, Olaparib. Advancement of LP184, potentially exploiting recurrent and actionable DDRG mutations, is anticipated to be translated into future clinical trials for mCRPC, a lethal CaP that is responsible for ~33,000 deaths/year in the US alone. Given that only a subset of patients responds to any single drug in this advanced CaP stage, LP184 stands out as a unique agent that may complement or synergize with drugs currently used in treatment of mCRPC and improve the outcomes for men with lethal CaP.

The frequency of determining pathogenic mutations in the genes in question was determined. The early detection of prostate cancer were organization for patient with with pathogenic mutations.

Patients harboring germline mutations tended to have earlier onset of AML (p = 0.005), however, the presence of germline mutations did not showed significant association with other clinical characteristics or treatment outcome. Since each mutation was rare, further study with a larger number of cases would be needed to establish the effect of the mutations.

One BRCA2-mutated patient treated by docetaxel was particularly long responder (PFS = 39.2 months)... Mutated mCRPC patients benefit from standard therapies, with long responders to taxanes among patients with BRCA1/2 and ATM mutations. Research Funding: None

P2, N=30, Recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial primary completion date: May 2020 --> May 2021