scholarly journals Somatic Tumor Profile Analysis in a Patient with Germline PMS2 Mutation and Synchronous Ovarian and Uterine Carcinomas

2021 ◽  
Vol 11 (7) ◽  
pp. 634
Author(s):  
Karen M. Huelsman ◽  
Jack B. Basil ◽  
Rebecca Sisson ◽  
Lindsay R. Lipe ◽  
Brett Mahon ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Lynch Syndrome ◽  
Profile Analysis ◽  
Common Site ◽  
Therapy Options ◽  
Biologically Relevant ◽  
Synchronous Cancers ◽  
Early Grade ◽  
Generation Sequencing ◽  
Tumor Profiling

Lynch syndrome patients with synchronous endometrial and ovarian cancer (SEOC) are rare. When these cases occur, they are most often endometrioid histology and early grade. Early-grade tumors are not often sent for somatic tumor profiling. We present a 39 year old SEOC patient with germline PMS2 Lynch syndrome and clinical tumor analysis leading to insight regarding the origin and cause of these tumors, with potential therapy options. PMS2-related SEOC is less common due to lower risks for these cancers associated with germline PMS2 mutation compared to other Lynch genes. While synchronous cancers are not common, they are more likely to occur with Lynch syndrome. Tumor profiling with next-generation sequencing of 648 genes identified sixteen shared somatic actionable and biologically relevant mutations. This case is a rare example of a patient with PMS2 germline Lynch syndrome with shared somatic variants that demonstrate clonality of the two tumors arising from one common site.

scholarly journals Assessing Genetic Variants in Matched Biocompartments From Patients With Serous Ovarian Cancer

2021 ◽  
Vol 20 ◽  
pp. 153303382110279
Author(s):  
Brooke E. Sanders ◽  
Lisa Ku ◽  
Paul Walker ◽  
Benjamin G. Bitler
Keyword(s):  
Ovarian Cancer ◽  
Genetic Variants ◽  
Mutant Allele ◽  
Serous Ovarian Cancer ◽  
Brca Testing ◽  
Panel Testing ◽  
University Of Colorado ◽  
Gene Panel Testing ◽  
The University ◽  
Tumor Profiling

The clinical use of molecular tumor profiling (MTP) is expanding and there is an increasing use of MTP data to manage patient care. At the University of Colorado, 18 patients were diagnosed with primary serous ovarian cancer between 9/2015 and 6/2019 and consented for banking and analysis of tumor, ascites and plasma. All 18 patients had tumor and plasma samples that were sent for MTP, and 13 of 18 patients additionally had ascites collected and sent for MTP. 50-gene panel testing and BRCA testing were performed on primary tumor. BRCA genetic variants were more likely to be identified in plasma as compared to ascites or tumor, though not statistically significant ( P = 0.17). Co-occurring genetic variants between plasma and ascites were less common in comparison to co-occurring variants between tumor and plasma or tumor and ascites, though not statistically significant ( P = 0.68). Variants in KDR (VEGFR2) and TP53 were most likely to be conserved across all 3 biocompartments. Mutant allele frequencies (MAF) of individual genetic variants varied across biocompartments, though tended to be highest in the tumor, followed by ascites.

Adoption of universal next generation sequencing for lynch syndrome screening in endometrial cancer

2022 ◽  
Vol 164 (1) ◽  
pp. 4-5
Author(s):  
Isabel Rodriguez ◽  
Sarah Strickland ◽  
David Wells ◽  
Enna Manhardt ◽  
Eric Konnick ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Next Generation Sequencing ◽  
Lynch Syndrome ◽  
Next Generation ◽  
Generation Sequencing

scholarly journals Integrating a Next Generation Sequencing Panel into Clinical Practice in Ovarian Cancer

2019 ◽  
Vol 60 (10) ◽  
pp. 914 ◽  
Author(s):  
Yong Jae Lee ◽  
Dachan Kim ◽  
Hyun-Soo Kim ◽  
Kiyong Na ◽  
Jung-Yun Lee ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Clinical Practice ◽  
Next Generation Sequencing ◽  
Next Generation ◽  
Generation Sequencing

scholarly journals Characteristics of Lynch syndrome associated ovarian cancer

2018 ◽  
Vol 150 (2) ◽  
pp. 324-330 ◽  
Author(s):  
J.M. Woolderink ◽  
G.H. De Bock ◽  
J.A. de Hullu ◽  
H. Hollema ◽  
R.P. Zweemer ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Lynch Syndrome

scholarly journals Understanding Inherited Risk in Unselected Newly Diagnosed Patients With Endometrial Cancer

2019 ◽  
pp. 1-15
Author(s):  
Karen A. Cadoo ◽  
Diana L. Mandelker ◽  
Semanti Mukherjee ◽  
Carolyn Stewart ◽  
Deborah DeLair ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Next Generation Sequencing ◽  
Lynch Syndrome ◽  
Microsatellite Instability ◽  
Mismatch Repair ◽  
Cancer Predisposition ◽  
Next Generation ◽  
Germline Variants ◽  
Predisposition Genes ◽  
Generation Sequencing

PURPOSE Mutations in DNA mismatch repair genes and PTEN, diagnostic of Lynch and Cowden syndromes, respectively, represent the only established inherited predisposition genes in endometrial cancer to date. The prevalence of other cancer predisposition genes remains unclear. We determined the prevalence of pathogenic germline variants in unselected patients with endometrial cancer scheduled for surgical consultation. PATIENTS AND METHODS Patients prospectively consented (April 2016 to May 2017) to an institutional review board–approved protocol of tumor-normal sequencing via a custom next-generation sequencing panel—the Memorial Sloan Kettering–Integrated Mutation Profiling of Actionable Cancer Targets—that yielded germline results for more than 75 cancer predisposition genes. Tumors were assessed for microsatellite instability. Per institutional standards, all tumors underwent Lynch syndrome screening via immunohistochemistry (IHC) for mismatch repair proteins. RESULTS Of 156 patients who consented to germline genetic testing, 118 (76%) had stage I disease. In 104 patients (67%), tumors were endometrioid, and 60 (58%) of those tumors were grade 1. Twenty-four pathogenic germline variants were identified in 22 patients (14%): seven (4.5%) had highly penetrant cancer syndromes and 15 (9.6%) had variants in low-penetrance, moderate-penetrance, or recessive genes. Of these, five (21%) were in Lynch syndrome genes (two MSH6, two PMS2, and one MLH1). All five tumors had concordant IHC staining; two (40%) were definitively microsatellite instability–high by next-generation sequencing. One patient had a known BRCA1 mutation, and one had an SMARCA4 deletion. The remaining 17 variants (71%) were incremental findings in low- and moderate-penetrance variants or genes associated with recessive disease. CONCLUSION In unselected patients with predominantly low-risk, early-stage endometrial cancer, germline multigene panel testing identified cancer predisposition gene variants in 14%. This finding may have implications for future cancer screening and risk-reduction recommendations. Universal IHC screening for Lynch syndrome successfully identifies the majority (71%) of high-penetrance germline mutations.

Letrozole in the management of advanced ovarian cancer: an old drug as a new targeted therapy

2020 ◽  
Vol 30 (7) ◽  
pp. 1058-1064
Author(s):  
Claudia Marchetti ◽  
Francesca De Felice ◽  
Raffaella Ergasti ◽  
Giovanni Scambia ◽  
Anna Fagotti
Keyword(s):  
Ovarian Cancer ◽  
Maintenance Treatment ◽  
Advanced Ovarian Cancer ◽  
Standard Of Care ◽  
Low Grade ◽  
Toxicity Profile ◽  
Biologically Relevant ◽  
Cancer Management ◽  
Free Interval ◽  
Optimal Setting

At present, there is no standard of care on the use of letrozole in ovarian cancer management. We performed a systematic review of the available literature addressing this issue. Data demonstrated a role for letrozole in ovarian cancer, in both the primary and recurrent setting. Letrozole, which has a favorable toxicity profile, seems to assure a prolonged recurrence-free interval, particularly when used as maintenance treatment, in low grade serous ovarian cancer; in recurrent cases it had also led to prolonged disease control. However, the optimal setting and biologically relevant patient population needs to be defined in larger trials.

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