Serrated pathway in colorectal carcinogenesis

Yamane, Letícia; Scapulatempo‐Neto, Cristovam; Reis, Rui Manuel; Guimarães, Denise Peixoto

doi:10.3748/wjg.v20.i10.2634

Cited by 95 publications

(90 citation statements)

References 51 publications

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“…Thus we now understand that the serrated pathway is a route through which 10-30% of CRC develop 14,15 . This was supported by a recent systematic review and meta-analysis, by Gao et al, revealing a strong positive relationship between proximal SP and synchronous advanced neoplasia 16 .…”

Section: Introductionmentioning

confidence: 99%

Lifestyle Risk Factors for Serrated Colorectal Polyps: A Systematic Review and Meta-analysis

Bailie¹,

Loughrey²,

Coleman³

2017

Gastroenterology

142

127

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Section: Introductionmentioning

confidence: 99%

Lifestyle Risk Factors for Serrated Colorectal Polyps: A Systematic Review and Meta-analysis

Bailie¹,

Loughrey²,

Coleman³

2017

Gastroenterology

142

127

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“…However, EGFR, the target of these drugs, which is overexpressed in approximately 50.0–80.0% of CRC, failed to predict a therapeutic response when used clinically. Research showed that the Kirsten rat sarcoma viral oncogene homolog ( KRAS ) gene, an important member of the EGFR signalling cascade, can acquire activating mutations in exon 2 codons 12 and 13 in approximately 35.0–45.0% of the CRC cases, rendering EGFR inhibitors ineffective [4, 5]. In 2009, the US Food and Drug Administration (FDA) approved EGFR-targeted monoclonal antibody therapy with cetuximab and panitumumab in patients with metastatic colorectal cancer (mCRC) along with analysis of KRAS mutation status, which is a predictive biological marker of resistance [6–8].…”

Section: Introductionmentioning

confidence: 99%

The pattern of KRAS mutations in metastatic colorectal cancer: a retrospective audit from Sri Lanka

Sirisena

Deen

Mandawala³

et al. 2017

BMC Res Notes

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ObjectiveActivating mutations in the KRAS gene, found in approximately 53% of metastatic colorectal cancer (mCRC) cases, can render epidermal growth factor receptor (EGFR) inhibitors ineffective. Regional differences in these mutations have been reported. This is the first study which aims to describe the pattern of KRAS mutations in a Sri Lankan cohort of mCRC patients.ResultsThe KRAS genotypes detected in mCRC patients which have been maintained in an anonymized database were retrospectively analyzed. Of the 108 colorectal tissue samples tested, 25 (23.0%) had KRAS mutations. Overall, there were 68 (63.0%) males and 40 (37.0%) females. Among the KRAS positive cases, there were 14 (56.0%) males and 11 (44.0%) females. Their age distribution ranged from 29 to 85 years with a median age of 61 years. There were 15 patients (60.0%) with point mutations in codon 12 while 10 (40.0%) had a single mutation in codon 13. The most common KRAS mutation identified was p.Gly13Asp (40.0%), followed by p.Gly12Val (24.0%). Other mutations included p.Gly12Cys (12.0%), p.Gly12Ser (12.0%), p.Gly12Asp (8.0%), and p.Gly12Arg (4.0%). The codon 13 mutation was a G>A transition (40.0%), while G>T transversions (32.0%), G>A transitions (24.0%), and G>C transversions (4.0%) were found in the codon 12 mutations. The frequency of KRAS mutations was similar to that reported for Asian patients. However, in contrast to several published studies, the G>A transition in codon 12 (c.35G>A; p.Gly12Asp), was not the most common mutation within codon 12 in our cohort. This may be a reflection of the genetic heterogeneity in the pattern of KRAS mutations in mCRC patients but valid conclusions cannot be drawn from these preliminary findings due to the small size of the study sample.

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“…Adenoma is the principal precursor lesion of CRC (5,6) but, recently, serrated polyp was recognized as an alternative precursor lesion of CRC and follows an alternative pathway in which serrated polyp replaces the traditional adenoma as the precursor lesion to serrated CRC, accounting for ~10% of all CRCs (7,8). Serrated polyps form a heterogeneous group of colorectal lesions that include hyperplastic polyps (HPs), sessile serrated adenoma (SSA), traditional serrated adenoma (TSA) and a combination of two or more characteristics, formerly classified as mixed polyps (MP) (9). HPs are the most common serrated polyp and they have been increasingly suggested to be precursor lesions, since they may develop into other serrated polyps as SSA, TSA or MP to CRC (10).…”

Section: Introductionmentioning

confidence: 99%

KRAS and BRAF mutations and MSI status in precursor lesions of colorectal cancer detected by colonoscopy

et al. 2014

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Abstract. Colorectal cancer (CRC) is one of the most frequent cancers worldwide. Adenoma is the main precursor lesion and, recently, the serrated polyps were described as a group of colorectal lesions with malignant potential. The morphologic and biologic characterizations of serrated polyps remain limited. The aim of the present study was to determine the frequency of KRAS and BRAF mutations and microsatellite instability (MSI) in CRC precursor lesions, to evaluate the association between molecular, pathologic and morphologic alterations in precursor lesions and to compare with the alterations detected in CRC. A series of 342 precursor lesions were removed from 155 patients during colonoscopy. After morphologic classification, molecular analysis was performed in 103 precursor lesions, and their genetic profile compared with 47 sporadic CRCs. Adenomas were the main precursor lesions (70.2%). Among the serrated polyps, the main precursor lesion was hyperplastic polyps (HPs) (82.4%), followed by sessile serrated adenomas (12.7%) and traditional serrated adenomas (2.0%). KRAS mutations were detected in 13.6% of the precursor lesions, namely in adenomas and in HPs, but in no serrated adenoma. BRAF mutations were found in 9 (8.7%) precursor lesions, mainly associated with serrated polyps and absent in adenomas (P<0.001). High MSI (MSI-H) was absent in precursor lesions. In the 47 CCR cases, 46.8% exhibited KRAS mutation, 6.5% BRAF mutations and 10.6% MSI-H. This study confirms the role of KRAS and BRAF mutations in CRC carcinogenesis, a crucial step in implementing CRC screening strategies.

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Serrated pathway in colorectal carcinogenesis

Cited by 95 publications

References 51 publications

Lifestyle Risk Factors for Serrated Colorectal Polyps: A Systematic Review and Meta-analysis

Lifestyle Risk Factors for Serrated Colorectal Polyps: A Systematic Review and Meta-analysis

The pattern of KRAS mutations in metastatic colorectal cancer: a retrospective audit from Sri Lanka

KRAS and BRAF mutations and MSI status in precursor lesions of colorectal cancer detected by colonoscopy

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