FrequentBRAFmutation in early-onset colorectal cancer in Taiwan: association with distinct clinicopathological and molecular features and poor clinical outcome

2015 ◽  
Vol 69 (4) ◽  
pp. 319-325 ◽  
Author(s):  
Jia-Huei Tsai ◽  
Jau-Yu Liau ◽  
Yu-Lin Lin ◽  
Li-Hui Tseng ◽  
Liang-In Lin ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Clinical Outcome ◽  
Early Onset ◽  
Poor Clinical Outcome ◽  
Molecular Features ◽  
Early Onset Colorectal Cancer

scholarly journals Molecular Features and Methylation Status in Early Onset (≤40 Years) Colorectal Cancer: A Population Based, Case-Control Study

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Giulia Magnani ◽  
Daniela Furlan ◽  
Nora Sahnane ◽  
Luca Reggiani Bonetti ◽  
Federica Domati ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Mismatch Repair ◽  
Early Onset ◽  
Methylation Status ◽  
The Elderly ◽  
Population Based ◽  
Repair System ◽  
Molecular Features ◽  
A Minor ◽  
Early Onset Colorectal Cancer

Colorectal cancer is usually considered a disease of the elderly. However, a small fraction of patients develops colorectal cancer earlier. The aim of our study was to define the frequency of known hereditary colorectal syndromes and to characterise genetic and epigenetic features of early nonhereditary tumors. Thirty-three patients ≤40 years with diagnosis of colorectal cancer and 41 patients with disease at >60 years of age were investigated for MSI, Mismatch Repair proteins expression,KRASandBRAFmutations, hypermethylation, and LINE-1 hypomethylation. Detection of germline mutations was performed in Mismatch Repair,APCandMUTYHgenes. Early onset colorectal cancer showed a high incidence of hereditary forms (18%).KRASmutations were detected in 36% of early nonhereditary tumors. Early onset colorectal cancer disclosed an average number of methylated genes significantly lower when compared to the controls (p=0.02). Finally both of the two groups were highly methylated inESR1,GATA5, andWT1genes and were similar for LINE-1 hypomethylation. The genetic make-up of carcinomas differs from young to elderly patients. Early onset tumors showed more frequently a constitutional defective of Mismatch Repair System and a minor number of methylated genes. Hypermethylation ofESR1,GATA5, andWT1genes suggests possible markers in the earlier diagnosis of colorectal tumorigenesis.

Su1729 EARLY-ONSET COLORECTAL CANCER HAS UNIQUE CLINICAL CHARACTERISTICS AND MOLECULAR FEATURES

2019 ◽  
Vol 89 (6) ◽  
pp. AB398
Author(s):  
Rawan Dayah ◽  
Mohammad Bilal ◽  
Nattapron Tun ◽  
Tewfeek K. Abu-Shami ◽  
Adam L. Booth ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Early Onset ◽  
Clinical Characteristics ◽  
Molecular Features ◽  
Early Onset Colorectal Cancer

scholarly journals Association of Polyps with Early-Onset Colorectal Cancer and Throughout Surveillance: Novel Clinical and Molecular Implications

Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1900
Author(s):  
José Perea García ◽  
Julia Arribas ◽  
Ángel Cañete ◽  
Juan Luis García ◽  
Edurne Álvaro ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Early Onset ◽  
Comparative Genomic ◽  
Molecular Features ◽  
Mucinous Component ◽  
History Of ◽  
Advanced Stages ◽  
The Right ◽  
Early Onset Colorectal Cancer

Early-onset colorectal cancer (EOCRC) is an increasing and worrisome entity. The aim of this study was to analyze its association with polyps concerning prognosis and surveillance. EOCRC cases were compared regarding the presence or absence of associated polyps (clinical and molecular features), during a minimum of 7 years of follow-up. Of 119 cases, 56 (47%) did not develop polyps (NP group), while 63 (53%) did (P group). The NP group showed a predominant location of the CRC in the rectum (50%), of sporadic cases (54%), and diagnosis at advanced stages: Only P53 and SMARCB1 mutations were statistically linked to this group. The P group, including mainly early-diagnosed tumors, was linked with the most frequent and differential altered chromosomal regions in the array comparative genomic hybridization. The two most frequent groups according to the follow-up were the NP group (40%), and patients developing polyps in the first 5 years of follow-up (P < 5FU) (34%) (these last groups predominantly diagnosed at the earliest stage and with adenomatous polyps (45%)). EOCRC with polyps that developed during the entire follow-up (PDFU group) were mainly located in the right colon (53%), diagnosed in earlier stages, and 75% had a familial history of CRC. Patients developing polyps after the first 5 years (P > 5FU) showed a mucinous component (50%). Our results show that the absence or presence of polyps in EOCRC is an important prognostic factor with differential phenotypes. The development of polyps during surveillance shows that it is necessary to extend the follow-up time, also in those cases with microsatellite-stable EOCRC.

scholarly journals Clinicopathological and Molecular Characteristics of Early-Onset vs Late-onset Colorectal Cancer according to Tumor Location

2021 ◽  
Author(s):  
Yongle Chen ◽  
Zexian Chen ◽  
Juanni Huang ◽  
Jiancong Hu ◽  
Xiaowen He ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Early Onset ◽  
Odds Ratio ◽  
Late Onset ◽  
Tumor Location ◽  
Molecular Characteristics ◽  
Molecular Features ◽  
Significant Difference ◽  
The Right ◽  
Early Onset Colorectal Cancer

Abstract BackgroundThe incidence of early-onset colorectal cancer (EOCRC) is rapidly increasing worldwide in decade when screening of colorectal cancer (CRC) is more prevalent. The clinicopathological and molecular characteristics of EOCRC have not yet been clarified. This study aims to evaluate clinicopathological and molecular features including status of deficiencies of mismatch repair (dMMR), mutation of PIK3CA, BRAF and KRAS among EOCRC and late-onset colorectal cancer (LOCRC) patients according to different tumor locations.MethodsWe identified CRC patients from a prospectively maintained CRC database between January 2015 and December 2018 at the Sixth Affiliated Hospital of Sun Yat-sen University. The clinicopathological and molecular characteristics including dMMR, mutation of PIK3CA, BRAF and KRAS were compared between EOCRC and LOCRC. The relationships according to different tumor locations were assessed.ResultsTotally 4468 patients, including 947 EOCRC patients and 3521 LOCRC patients, were analyzed in this study. Compared with LOCRC patients, EOCRC patients were more likely to have status of dMMR (odds ratio [OR], 2.52; 95% confidence interval [CI], 2.05-3.10; P<0.001), regardless of tumor location, so were loss of MSH2 and MSH6 (OR, 4.31; 95% CI, 2.86-6.48; P<0.001; OR, 3.40; 95% CI, 2.42-4.76; P<0.001, respectively). Loss of MLH1 and PMS2 were detected more frequently in EOCRC overall (OR, 2.11; 95% CI, 1.55-2.87; P<0.001; OR, 1.83; 95% CI, 1.42-2.35; P<0.001, respectively), but only in left-side and right-side colon rather than in rectum. EOCRC patients were more likely to be detected with mutation of PIK3CA (OR, 1.24; 95% CI, 1.01-1.53; P=0.041), which only trended to exist in the left-side colon (OR, 1.51; CI, 0.98-2.33; P=0.06), but not in the right-side colon or rectum. No significant difference was found for BRAF or KRAS mutation, but mutation of KRAS was more frequently found in left-side colon (OR, 1.34; CI, 1.02-1.77; P=0.04) among EOCRC patients.ConclusionsStatus of dMMR, mutation of PIK3CA, BRAF and KRAS were different between EOCRC and LOCRC patients according to different tumor locations, which implied that EOCRC might be a unique subgroup of CRC patients. Further investigations of molecular and genetic differences should be performed to help define new diagnosing and therapeutical strategies for EOCRC patients.

Su1008 CLINICAL AND PATHOLOGIC CHARACTERISTICS OF EARLY ONSET COLORECTAL CANCER (EOCRC).

2020 ◽  
Vol 158 (6) ◽  
pp. S-496
Author(s):  
Arif A. Arif ◽  
Daljeet Chahal ◽  
Caroline Speers ◽  
Mary A. De Vera ◽  
Sharlene Gill ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Early Onset ◽  
Early Onset Colorectal Cancer

scholarly journals High prevalence of TP53 loss and whole-genome doubling in early-onset colorectal cancer

2021 ◽  
Author(s):  
Jeong Eun Kim ◽  
Jaeyong Choi ◽  
Chang-Ohk Sung ◽  
Yong Sang Hong ◽  
Sun Young Kim ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Early Onset ◽  
Large Scale ◽  
Late Onset ◽  
Age Groups ◽  
The Cancer Genome Atlas ◽  
Whole Genome ◽  
Genome Doubling ◽  
Whole Genome Doubling ◽  
Early Onset Colorectal Cancer

AbstractThe global incidence of early-onset colorectal cancer (EO-CRC) is rapidly rising. However, the reason for this rise in incidence as well as the genomic characteristics of EO-CRC remain largely unknown. We performed whole-exome sequencing in 47 cases of EO-CRC and targeted deep sequencing in 833 cases of CRC. Mutational profiles of EO-CRC were compared with previously published large-scale studies. EO-CRC and The Cancer Genome Atlas (TCGA) data were further investigated according to copy number profiles and mutation timing. We classified colorectal cancer into three subgroups: the hypermutated group consisted of mutations in POLE and mismatch repair genes; the whole-genome doubling group had early functional loss of TP53 that led to whole-genome doubling and focal oncogene amplification; the genome-stable group had mutations in APC and KRAS, similar to conventional colon cancer. Among non-hypermutated samples, whole-genome doubling was more prevalent in early-onset than in late-onset disease (54% vs 38%, Fisher’s exact P = 0.04). More than half of non-hypermutated EO-CRC cases involved early TP53 mutation and whole-genome doubling, which led to notable differences in mutation frequencies between age groups. Alternative carcinogenesis involving genomic instability via loss of TP53 may be related to the rise in EO-CRC.

scholarly journals Non-Lynch Familial and Early-Onset Colorectal Cancer Explained by Accumulation of Low-Risk Genetic Variants

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3857
Author(s):  
Pilar Mur ◽  
Nuria Bonifaci ◽  
Anna Díez-Villanueva ◽  
Elisabet Munté ◽  
Maria Henar Alonso ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Risk Score ◽  
Early Onset ◽  
Low Risk ◽  
Polygenic Risk Score ◽  
Polygenic Risk ◽  
Pathogenic Variants ◽  
Predisposing Genes ◽  
The Mean ◽  
Early Onset Colorectal Cancer

A large proportion of familial and/or early-onset cancer patients do not carry pathogenic variants in known cancer predisposing genes. We aimed to assess the contribution of previously validated low-risk colorectal cancer (CRC) alleles to familial/early-onset CRC (fCRC) and to serrated polyposis. We estimated the association of CRC with a 92-variant-based weighted polygenic risk score (wPRS) using 417 fCRC patients, 80 serrated polyposis patients, 1077 hospital-based incident CRC patients, and 1642 controls. The mean wPRS was significantly higher in fCRC than in controls or sporadic CRC patients. fCRC patients in the highest (20th) wPRS quantile were at four-fold greater CRC risk than those in the middle quantile (10th). Compared to low-wPRS fCRC, a higher number of high-wPRS fCRC patients had developed multiple primary CRCs, had CRC family history, and were diagnosed at age ≥50. No association with wPRS was observed for serrated polyposis. In conclusion, a relevant proportion of mismatch repair (MMR)-proficient fCRC cases might be explained by the accumulation of low-risk CRC alleles. Validation in independent cohorts and development of predictive models that include polygenic risk score (PRS) data and other CRC predisposing factors will determine the implementation of PRS into genetic testing and counselling in familial and early-onset CRC.

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