scholarly journals The repertoire of germline variants in patients with early‐onset rectal cancer

2022 ◽  
Author(s):  
Caroline Moraes Beltrami ◽  
Luisa Matos do Canto ◽  
Rolando André Rios Villacis ◽  
Annabeth Høgh Petersen ◽  
Mads Malik Aagaard ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Early Onset ◽  
Germline Variants

scholarly journals Prevalence of RECQL germline variants in Pakistani early-onset and familial breast cancer patients

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Muhammad Usman Rashid ◽  
Noor Muhammad ◽  
Faiz Ali Khan ◽  
Umara Shehzad ◽  
Humaira Naeemi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Early Onset ◽  
Familial Breast Cancer ◽  
High Performance ◽  
Breast Cancer Patients ◽  
Germline Variants ◽  
Variants Of Unknown Significance ◽  
Breast Cancer Predisposition ◽  
Novel Variants

Abstract Background The RecQ Like Helicase (RECQL) gene has previously been shown to predispose to breast cancer mainly in European populations, in particular to estrogen receptor (ER) and/or progesterone receptor (PR) positive tumor. Here, we investigated the contribution of pathogenic RECQL germline variants to hereditary breast cancer in early-onset and familial breast cancer patients from Pakistan. Methods Comprehensive RECQL variant analysis was performed in 302 BRCA1 and BRCA2 negative patients with ER and/or PR positive breast tumors using denaturing high-performance liquid chromatography followed by DNA sequencing. Novel variants were classified using Sherloc guidelines. Results One novel pathogenic protein-truncating variant (p.W75*) was identified in a 37-year-old familial breast cancer patient. The pathogenic variant frequencies were 0.3% (1/302) in early-onset and familial breast cancer patients and 0.8% (1/133) in familial patients. Further, three novel variants of unknown significance, p.I141F, p.S182S, and p.C475C, were identified in familial breast cancer patients at the age of 47, 68, and 47 respectively. All variants were absent in 250 controls. Conclusions Our data suggest that the RECQL gene plays a negligible role in breast cancer predisposition in Pakistan.

scholarly journals Exome sequencing identifies ARID2 as a novel tumor suppressor in early-onset sporadic rectal cancer

2020 ◽  
Author(s):  
Pratyusha Bala ◽  
Anurag Kumar Singh ◽  
Padmavathi Kavadipula ◽  
Viswakalyan Kotapalli ◽  
Radhakrishnan Sabarinathan ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Tumor Suppressor ◽  
Exome Sequencing ◽  
Early Onset ◽  
Target Genes ◽  
Ectopic Expression ◽  
Tumor Formation ◽  
Inhibition Of Growth ◽  
Sporadic Rectal Cancer ◽  
And Migration

AbstractEarly-onset sporadic rectal cancer (EOSRC) is a unique and predominant colorectal cancer (CRC) subtype in India. In order to understand the tumorigenic process in EOSRC, we performed whole exome sequencing of 47 microsatellite stable EOSRC samples. Signature 1 was the predominant mutational signature in EOSRC, as previously shown in other CRC exome studies. More importantly, we identified TP53, KRAS, APC, PIK3R1 and SMAD4 as significantly mutated (q<0.1) and ARID1A and ARID2 as near-significantly mutated (restricted hypothesis testing; q<0.1) candidate drivers. Unlike the other candidates, the tumorigenic potential of ARID2, encoding a component of the SWI/SNF chromatin remodeling complex, is largely unexplored in CRC. shRNA mediated ARID2 knockdown performed in two different CRC cell lines resulted in significant alterations in transcript levels of cancer-related target genes. More importantly, ARID2 knockdown promoted several tumorigenic features including cell viability, proliferation, ability to override contact inhibition of growth, and migration besides significantly increasing tumor formation ability in nude mice. The observed gain in tumorigenic features were rescued upon ectopic expression of ARID2. Analyses of the TCGA CRC dataset revealed poorer survival in patients with ARID2 alterations. We therefore propose ARID2 as a novel tumor suppressor in CRC.

scholarly journals Germline variants in POLE are associated with early onset mismatch repair deficient colorectal cancer

2014 ◽  
Vol 23 (8) ◽  
pp. 1080-1084 ◽  
Author(s):  
Fadwa A Elsayed ◽  
C Marleen Kets ◽  
Dina Ruano ◽  
Brendy van den Akker ◽  
Arjen R Mensenkamp ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Mismatch Repair ◽  
Early Onset ◽  
Germline Variants

Molecular Features and Functional Implications of Germline Variants in Triple-Negative Breast Cancer

2020 ◽  
Author(s):  
Ding Ma ◽  
Si-Yu Chen ◽  
Jin-Xiao Ren ◽  
Yu-Chen Pei ◽  
Cong-Wei Jiang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Early Onset ◽  
Triple Negative ◽  
Parp Inhibitors ◽  
Chinese Patients ◽  
Molecular Characteristics ◽  
Germline Variants ◽  
Molecular Features ◽  
Germline Variant

Abstract Background The germline variant spectrum of triple-negative breast cancer (TNBC) is different from that of other subtypes and has demonstrated ethnic differences. However, the germline variants of TNBC among Chinese patients and its clinical significance remain unclear. Methods Using our multi-omics TNBC cohort (n = 325), we determined the spectrum of germline variants in TNBC and aimed to illustrate their biological and clinical implications. Results Overall, 16.0% (52 of 325) of TNBC patients harbored at least 1 pathogenic or likely pathogenic germline variant. These germline variants were associated with early onset of TNBC, the occurrence of contralateral breast cancer, the basal-like immune-suppressed mRNA subtype, and the homologous recombination deficiency (HRD) mutation subtype. Somatic allele-specific imbalance was observed in 54.1% of these germline variants, which was correlated with early onset of breast cancer and elevated HRD. The genes BRCA1 (7.4%), RAD51D (2.8%), and BRCA2 (2.2%) were those most frequently mutated. The RAD51D germline variants, especially K91fs, were enriched in Chinese patients with TNBC compared with Caucasian and African American patients. The Chinese-specific RAD51D germline variants were functionally associated with the instability of the RAD51D protein, HRD, and sensitivity to PARP inhibitors. Conclusions Chinese TNBC patients have a distinct spectrum of germline variants, with a remarkable impact on the clinical and molecular characteristics of the tumor. Integrative germline-somatic analysis may help identify TNBC patients who are most likely to be affected by their germline variants and in performing clinical interventions more precisely. The RAD51D variants enriched in our cohort may serve as therapeutic targets and guide precision treatment of TNBC.

Abstract 1198: Presence of non-canonical tumorigenesis pathways in early-onset sporadic rectal cancer.

2013 ◽  
Author(s):  
Ratheesh Raman ◽  
Viswakalyan Kotapalli ◽  
Raju SR Adduri ◽  
Vasantha Kumar Bhaskara ◽  
Swarnalata Gowrishankar ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Early Onset ◽  
Sporadic Rectal Cancer

scholarly journals Increasing Incidence of Colorectal Cancer in Young Adults

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Holli A. Loomans-Kropp ◽  
Asad Umar
Keyword(s):  
Colorectal Cancer ◽  
Rectal Cancer ◽  
Early Onset ◽  
Population Level ◽  
Distal Colon ◽  
Incidence Rates ◽  
Anatomical Distribution ◽  
Colon Cancers ◽  
Age Related ◽  
Incidence And Mortality

Background. Colorectal cancer (CRC) incidence and mortality has been declining in the U.S. Despite success in reducing CRC incidence, incidence of early-onset CRC has increased markedly. In this study, we identified age-related disparities in CRC incidence and mortality, and investigated differences in anatomical distribution of colon cancers between populations. Methods. CRC trends were evaluated using Surveillance, Epidemiology, and End Results Program Data from 1980–2016 for individuals under age 50 and 50 years and older. Rates and ratios were calculated using SEER∗Stat. Regression analyses were calculated using Joinpoint. Results. Increased CRC incidence among individuals under age 50 was observed. Among individuals under age 50, incidence-based mortality (IBM) stabilized, while incidence and IBM decreased for individuals aged 50 years and older. Normalized trends indicated increased rectal cancer incidence for individuals under age 50, particularly among individuals aged 30–39. Similar incidence of proximal and distal colon cancers in individuals under age 50 was observed, while colon cancers in individuals aged 50 and older were primarily distal. Conclusions. We found age-related disparities in CRC incidence and IBM between individuals under age 50 and age 50 years and older. Increasing incidence rates of rectal cancer substantially accounts for this disparity among individuals under age 50. The escalating trends of early-onset CRC warrant investigation into the factors leading to the population-level trends.

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