PMS2 mutation

By comparing the gene mutation rates between the two cohorts, we identified that the mutation rates of MET, GNAS, PMS2, and PTCH1 genes were significantly higher in cystic LUAD compared to cystic LUAD. Our retrospective study has provided useful information about the clinical and molecular characteristics of LCCA, enhancing our understanding of its features for medical research and practice.

MMR-m GECs showed improved overall survival compared to MMR-wt (p = 0.009), a relationship not observed in other tumor types. This study demonstrates that the MMR spectrum is extremely hetoerogeneous in solid tumors, highliting the need for comprehensive and tumor-specific testing strategies.

This case illustrates how effective AK104/Cadonilimab (a PD-1/CTLA-4 bispecific) can be when combined with albumin-bound paclitaxel for treating advanced UCCC, especially in patients who have not responded to standard therapies. The patient's complete and lasting response shows the potential of PD-1/CTLA-4 bispecific immunotherapy. This suggests that cadonilimab could provide important clinical benefits for patients with advanced or recurrent UCCC.

P=N/A, N=240, Recruiting, M.D. Anderson Cancer Center | Active, not recruiting --> Recruiting

During adjuvant treatment with carboplatin and paclitaxel regimen, control CT imaging demonstrated inguinal and hepatic metastases...Subsequent treatment with cyclophosphamide and bevacizumab was initiated, comprising eight and nine cycles, respectively. Despite these efforts, the malignancy remained refractory, ultimately leading to the patient's death 18 months post-diagnosis.Conclusion This case highlights the significant therapeutic resistance encountered in synchronous gynecological cancers, particularly when compounded by hereditary genetic mutations. Given the incidence of synchronous tumors and the critical role of MMR genes, there is an urgent need for innovative, personalized treatment strategies to effectively manage such complex cases.

Treatment involved surgery and chemotherapy for the older brother, emphasizing the importance of genetic testing for siblings with a cancer family history. NGS plays a pivotal role in identifying genetic mutations and guiding treatment decisions, demonstrating its significance in managing LS and other hereditary cancers.

P=N/A, N=247, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting | N=80 --> 247

A total of seven major clones of NRAS [five] and NT5C2 [two] were noted in six out of 14 (43%) relapse patients, accounting for 44% of early relapses. In addition, 10 minor clones (PMS2 [two], NRAS [four], NT5C2 [three], and TP53 [one]) were noted in five out of 14 (36%) patients. In the 56 sequential therapy samples, six major clones were noted (NRAS [five], KRAS [one]) in four out of 14 (28.5%) patients, with two increasing in size in maintenance samples, leading to subsequent relapse in both cases. In addition, therapy-acquired minor clones in NT5C2 [four] and PMS2 [one] were seen to emerge in maintenance samples in four out of 14 (28.5%) patients, with concordant detection of such major and minor clones in unpaired relapse samples, indicating the need for their active surveillance during therapy. Overall, digital PCR validated NRAS and NT5C2 major clones in one-third (10 out of 27; 37%) of cases, driving nearly half of early relapses.

The drafting of the guidelines was organized by the Oncogenetics Working Group of the Society for Medical Genetics and Genomics of J. E. Purkyně Czech Medical Society, in cooperation with representatives of oncology, oncogynecology, and gastroenterology. The guidelines are based on the current recommendations of the National Comprehensive Cancer Network (NCCN), European Society of Medical Oncology (ESMO) and take into account the capacity of the Czech healthcare system.

P1/2, N=60, Active, not recruiting, National Cancer Institute (NCI) | Recruiting --> Active, not recruiting

P=N/A, N=1395, Recruiting, Beth Israel Deaconess Medical Center | N=500 --> 1395 | Trial completion date: Mar 2028 --> Dec 2032 | Trial primary completion date: Mar 2027 --> Dec 2032

P=N/A, N=419, Active, not recruiting, Mayo Clinic | N=2000 --> 419