Declining Detection Rates for APC and Biallelic MUTYH Pathogenic Variants in Polyposis Patients, Implications for DNA Testing Policy

2019 ◽  
Author(s):  
Diantha Terlouw ◽  
Manon Suerink ◽  
Sunny Singh ◽  
J. T. van Wezel ◽  
J. J. P. Gille ◽  
...  
Keyword(s):  
Dna Testing ◽  
Detection Rates ◽  
Pathogenic Variants

scholarly journals Germline variants and phenotypic spectrum in a Canadian cohort of individuals with diffuse gastric cancer

2019 ◽  
Vol 27 (2) ◽  
Author(s):  
M. Aronson ◽  
C. Swallow ◽  
A. Govindarajan ◽  
K. Semotiuk ◽  
Z. Cohen ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Detection Rate ◽  
Gene Panel ◽  
Diffuse Gastric Cancer ◽  
Cancer Syndrome ◽  
Detection Rates ◽  
Inherited Cancer ◽  
Panel Testing ◽  
Pathogenic Variants ◽  
Gene Panel Testing

Background CDH1 pathogenic variants (PV) cause the majority of inherited diffuse-gastric cancer (DGC), but have low detection rates and vary geographically. This study examines hereditary causes of DGC in patients from Ontario, Canada. Methods Eligible DGC cases at the Zane Cohen Centre (ZCC) underwent multi-gene panel or CDH1 single-site testing if they met 2015 International Gastric Cancer Linkage Consortium (IGCLC) criteria, isolated DGC <50 or family history suggestive of an inherited cancer syndrome. A secondary aim was to review all CDH1 families at the ZCC to assess cancer penetrance. Results 85 DGC patients underwent CDH1 (n=43) or multi-gene panel testing (n=42), and 15 (17.6%) PV or likely PV were identified.  CDH1 detection rate was 9.4% (n=8/85), and 11% (n=7/65) using IGCLC criteria.  No CDH1 PV identified in isolated DGC <40, but one PV identified in isolated DGC<50.  Multi-gene panel from 42 individuals identified 9 PV (21.4%) including CDH1, STK11, ATM, BRCA2, MLH1 and MSH2.  Review of 81 CDH1 carriers revealed that 10% had DGC (median age:48, range:38-59), 41% were unaffected (median age:53, range:26-89).  Three families had lobular-breast cancer (LBC) only.  Non-DGC/LBC malignancies included colorectal, gynecological, kidney/bladder, prostate, testicular and ductal breast. Conclusions Low detection rate of CDH1 in Ontario DGC patients.  No CDH1 PV found in isolated DGC <40, but identified in isolated DGC<50. Multi-gene panels are recommended for all DGC under age 50, and those meeting the IGCLC criteria, given overlapping phenotype with other hereditary conditions. HDGC phenotype is evolving with a spectrum of non-DGC/LBC cancers.

scholarly journals Declining detection rates for APC and biallelic MUTYH variants in polyposis patients, implications for DNA testing policy

2019 ◽  
Vol 28 (2) ◽  
pp. 222-230
Author(s):  
Diantha Terlouw ◽  
Manon Suerink ◽  
Sunny S. Singh ◽  
Hans J. J. P. Gille ◽  
Frederik J. Hes ◽  
...  
Keyword(s):  
Dna Testing ◽  
Detection Rates

High Detection Rates of Colorectal Neoplasia by Stool DNA Testing With a Novel Digital Melt Curve Assay

2009 ◽  
Vol 136 (2) ◽  
pp. 459-470 ◽  
Author(s):  
Hongzhi Zou ◽  
William R. Taylor ◽  
Jonathan J. Harrington ◽  
Fareeda Taher Nazer Hussain ◽  
Xiaoming Cao ◽  
...  
Keyword(s):  
Colorectal Neoplasia ◽  
Dna Testing ◽  
Detection Rates ◽  
High Detection ◽  
Stool Dna ◽  
Stool Dna Testing

Sa1042 MULTI-TARGET STOOL DNA TESTING ENRICHES DETECTION OF COLORECTAL NEOPLASIA BY COLONOSCOPY BUT YIELD IS INFLUENCED BY BASELINE POLYP DETECTION RATES

2019 ◽  
Vol 89 (6) ◽  
pp. AB149-AB150 ◽  
Author(s):  
Derek Ebner ◽  
Jason Eckmann ◽  
Kelli N. Burger ◽  
Douglas W. Mahoney ◽  
Mary E. Devens ◽  
...  
Keyword(s):  
Colorectal Neoplasia ◽  
Dna Testing ◽  
Polyp Detection ◽  
Detection Rates ◽  
Stool Dna ◽  
Stool Dna Testing

Prevalence of BRCA1/2 pathogenic variants in triple negative breast cancer patients stratified according to age at diagnosis.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e13677-e13677
Author(s):  
Ana Blatnik ◽  
Marta Banjac ◽  
Ksenija Strojnik ◽  
Simona Hotujec ◽  
Vida Stegel ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Genetic Testing ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Age At Diagnosis ◽  
Breast Cancer Patients ◽  
Detection Rates ◽  
Mutational Spectrum ◽  
Pathogenic Variants ◽  
Brca1 Brca2

e13677 Background: Triple negative breast cancer (TNBC) is strongly associated with germline BRCA1 pathogenic/likely pathogenic variants (PV/LPVs), with up to 28% TNBC patients being BRCA1 PV/LPV carriers. More recently, PALB2 variants have also been shown to be associated with TNBC. Genetic testing in Slovenian hereditary breast and ovarian cancer (HBOC) patients yields consistently high BRCA1/2 detection rates. Four BRCA1 PVs are particularly common, suggesting possible founder effects. Our aim was to analyze the results of panel based genetic testing in Slovenian TNBC patients, with an emphasis on BRCA1/BRCA2 mutational spectrum and detection rates depending on age at diagnosis. Methods: We evaluated the results of genetic testing, performed using a multi-gene panel in 1000 consecutive breast cancer cases. Only 210 patients with TNBC were included in further analysis. We analyzed the mutational spectrum and BRCA1/2 detection rates in TNBC patients stratified according to age at diagnosis. Results: In 80/210 (38.1%) TNBC patients PV/LPVs in BRCA1/2 were identified. Of these, the majority (74/80) were BRCA1-positive. The following variants: c.181T > G, c.5266dupC, c.1687C > T, and c.844_850dupTCATTAC were identified in 64.4% of BRCA1 carriers. BRCA1/2 detection rate decreased with age at diagnosis but was still 18.2% after age 60 (for BRCA1/2 detection rates stratified according to age at diagnosis see table). In 12/210 (5.7%) TNBC patients PV/LPVs in three other genes were identified (3.3% PALB2, 1.4% CHEK2, and 1% ATM). Conclusions: Prevalence of PVs in BRCA1 appears very high in Slovenian TNBC patients and warrants further population-based allele frequency studies with implications for future population screening. High rates of BRCA1/BRCA2 PVs in patients older than 60 years at diagnosis justify testing all TNBC patients, especially in view of treatment options which now include PARP inhibitors. PALB2 was the second most commonly mutated gene in our patients. [Table: see text]

Cancer surveillance in adults with germline TP53 pathogenic variants: A single-center observational study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 10530-10530
Author(s):  
Thomas Meyskens ◽  
Vincent Vandecaveye ◽  
Steven Pans ◽  
Raphaëla Dresen ◽  
Chantal Van Ongeval ◽  
...  
Keyword(s):  
Overall Survival ◽  
Cancer Detection ◽  
False Positive ◽  
Brain Mri ◽  
Cancer Surveillance ◽  
Premalignant Lesions ◽  
Whole Body ◽  
First Year ◽  
Detection Rates ◽  
Pathogenic Variants

10530 Background: Germline pathogenic variants (PV) in the tumor suppressor gene TP53 are associated with a high risk of developing diverse malignancies, often at young age, and predispose to Li-Fraumeni syndrome (LFS). Surveillance programs for presymptomatic PV carriers have shown survival benefit in a non-randomized trial. Here we describe the surveillance findings and clinical outcomes of adults with TP53 PV undergoing a standardized screening protocol. Methods: We identified adults with germline PV in TP53 who underwent surveillance at the University Hospitals Leuven, Belgium, between 04/2013 and 08/2020. Patients with prior cancer were allowed, while patients with an active malignancy requiring treatment at diagnosis of the TP53 PV were excluded. Surveillance was performed per modified Toronto protocol, including annual whole body diffusion-weighted MRI (WB-DWI/MRI), brain MRI, abdominal ultrasound (US), endoscopic surveillance, laboratory tests, dermatological examination and breast MRI/US in females. The primary aim was to evaluate the number and type of malignancies and premalignant lesions diagnosed during screening and to assess the proportion of malignancies detected by surveillance. Secondary outcomes were the cancer detection rate during the first year of screening, the proportion of carriers with false-positive findings, and overall survival. Results: We included 42 adults from 20 apparently unrelated families. Median age was 38y (range, 17-70y) and 23 had a history of prior cancer. After a median follow-up of 41.5mo, we diagnosed 18 cancers in 12/42 participants (29%). Overall survival was 95% in all participants, including 2 carriers who opted to discontinue surveillance. Surveillance detected 10/18 cancers (56%), the majority of whom through WB-DWI/MRI (6/10; 60%). No malignancies were identified with brain MRI. In 5/42 individuals (12%), surveillance detected a malignancy during the first year of screening. Only 2/10 cancers discovered with surveillance (1 soft tissue and 1 bone sarcoma) belong to the LFS core tumors. Cancers not detected with surveillance (8/18) were 6 non-melanoma skin cancers and 2 interval cancers (sarcoma post radiation, secondary acute leukemia). Additionally, we detected 27 premalignant lesions in 11/42 patients (26%), of whom 78% were diagnosed by colonoscopy. False-positive findings occurred in 7/42 patients (17%) and were mostly seen with WB-DWI/MRI. Conclusions: Adults with germline PV in TP53 that undergo surveillance have high cancer detection rates. The majority of malignancies were asymptomatic at diagnosis and detected with WB-DWI/MRI. Despite the high cancer incidence, few LFS core cancers were diagnosed and survival was encouraging. Increased genetic testing changes the clinical picture of germline TP53 carrier populations, justifying the transition from LFS to a wider concept of heritable TP53-related cancer syndrome.

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