Emerging concepts in colorectal neoplasia

Jass, Jeremy R.; Whitehall, Vicki; Young, Joanne; Leggett, Barbara A.

doi:10.1053/gast.2002.35392

Cited by 435 publications

(401 citation statements)

References 103 publications

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“…Approximately half of all cancers have mutated TP53 4, 5. In addition, mutation of the TP53 gene is found in 60–80% of CRCs 4, 5, 7. Mutation of the TP53 gene is a representative event during the progression of CRC 4, 5, 23, 24.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, mutation of KRAS is thought to be a critical genetic event in colorectal carcinogenesis 4, 6, 7, 2326.…”

Section: Discussionmentioning

confidence: 99%

“…Based on different forms of genomic instability, sporadic CRC can broadly be divided into two groups: the microsatellite instability (MIN; MSI) type, caused by MLH1 methylation of the promoter region, and the chromosome instability (CIN) type, characterized by genomic instability at the gross chromosomal level 3, 4, 5. The majority of sporadic CRCs (∼90%) are classified into the CIN type, whereas only approximately 10% of sporadic CRCs are classified into the MIN type 3, 4, 5, 6, 7. In addition, the microsatellite stable (MSS) type, which is similar to CIN, is also important in colorectal carcinogenesis.…”

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confidence: 99%

“…In addition, the microsatellite stable (MSS) type, which is similar to CIN, is also important in colorectal carcinogenesis. Studies have shown that MSI and MSS are mutually exclusive and are also used as basic molecular classification 3, 7…”

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confidence: 99%

“…However, the MSS phenotype is the main molecular phenotype in both LC and RC 10, 11. Previous reports have shown that the MSS phenotype is found in approximately 60–70% of RC and around 90% of LC 3, 7. To identify the molecular or clinicopathological differences between LC and RC, we must examine the molecular or clinicopathological differences in the MSS phenotype between LC and RC, given that the MSS phenotype is common in CRC.…”

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confidence: 99%

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Molecular differences in the microsatellite stable phenotype between left‐sided and right‐sided colorectal cancer

Takahashi

Sugai

Habano

et al. 2016

Intl Journal of Cancer

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Differences in the pathogenesis of microsatellite stable (MSS) sporadic colorectal cancers (CRCs) between left‐sided CRC (LC) and right‐sided CRC (RC) have not been clarified. To identify pathogenesis‐related genomic differences between MSS CRCs within the two locations, we performed a comprehensive molecular analysis using crypt isolation with samples from 92 sporadic CRCs. Microsatellite instability (MSI; high and low/negative) and DNA methylation status (low methylation epigenome; intermediate methylation epigenome [IME] or high methylation epigenome [HME]) were determined using polymerase chain reaction (PCR) microsatellite analysis and PCR‐bisulfite pyrosequencing, respectively. Additionally, mutations in the TP53, KRAS, BRAF and PIK3CA genes were examined using PCR‐bisulfite pyrosequencing (for KRAS and BRAF mutations) or PCR‐single conformation polymorphism (for TP53 and PIK3CA mutations), followed by sequencing of aberrant bands. Finally, a genome‐wide study using a copy number alteration (CNA)‐targeted single nucleotide polymorphism array was performed. Ninety‐two CRCs were classified into 71 MSS and 21 MSI phenotypes. We examined 71 CRCs with the MSS phenotype (LC, 56; RC, 15). Mutations in KRAS were associated with RC with the MSS phenotype, whereas mutations in TP53 were more frequently found in LC with the MSS phenotype. There were significant differences in the frequencies of KRAS and TP53 mutations in the IME between LC and RC with the MSS phenotype. Although CNA gains were associated with LC with the MSS phenotype, CNA losses were not major alterations associated with the MSS phenotype. These findings suggested that the molecular pathogenesis of the MSS phenotype in LC was different from that in RC.

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Section: Discussionmentioning

confidence: 99%

“…Therefore, mutation of KRAS is thought to be a critical genetic event in colorectal carcinogenesis 4, 6, 7, 2326.…”

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Molecular differences in the microsatellite stable phenotype between left‐sided and right‐sided colorectal cancer

Takahashi

Sugai

Habano

et al. 2016

Intl Journal of Cancer

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Molecular Classification of Patients With Unexplained Hamartomatous and Hyperplastic Polyposis

Sweet¹

2005

JAMA

222

125

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Context Significant proportions of patients with hamartomatous polyposis or with hyperplastic/mixed polyposis remain without specific clinical and molecular diagnosis or present atypically. Assigning a syndromic diagnosis is important because it guides management, especially surveillance and prophylactic surgery. Objective To systematically classify patients with unexplained hamartomatous or hyperplastic/mixed polyposis by extensive molecular analysis in the context of central rereview of histopathology results. Design, Setting, and Patients Prospective, referral-based study of 49 unrelated patients from outside institutions (n=28) and at a comprehensive cancer center (n=21), conducted from May 2, 2002, until December 15, 2004. Germline analysis of PTEN, BMPR1A, STK11 (sequence, deletion), SMAD4, and ENG (sequence), specific exon screening of BRAF, MYH, and BHD, and rereview of polyp histology results were performed. Main Outcome Measures Molecular, clinical, and histopathological findings in patients with unexplained polyposis. Results Of the 49 patients, 11 (22%) had germline mutations. Of 14 patients with juvenile polyposis, 2 with early-onset disease had mutations in ENG, encoding endoglin, previously only associated with hereditary hemorrhagic telangiectasia; 1 had hemizygous deletion encompassing PTEN and BMPR1A; and 1 had an SMAD4 mutation. One individual previously classified with Peutz-Jeghers syndrome had a PTEN deletion. Among 9 individuals with an unknown hamartomatous polyposis, 4 had mutations in STK11 (1), BMPR1A (2), and SMAD4 (1). Of the 23 patients with hyperplastic/ mixed polyposis, 2 had PTEN mutations. Substantial discrepancies in histopathology results were seen. Conclusions Systematic molecular classification of 49 patients with unexplained hamartomatous or hyperplastic polyposis uncovered a potential novel susceptibility gene, ENG, for juvenile polyposis. Importantly, given the substantial proportion of patients found to have germline mutations, more extensive analysis of the known susceptibility genes is indicated. Rereview of histology results by a dedicated gastrointestinal pathologist should be considered routinely, as organ-specific surveillance rests on defining syndromic diagnosis.

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Unwinding the Heterogeneous Nature of Hamartomatous Polyposis Syndromes

Carethers¹

2005

JAMA

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Emerging concepts in colorectal neoplasia

Cited by 435 publications

References 103 publications

Molecular differences in the microsatellite stable phenotype between left‐sided and right‐sided colorectal cancer

Molecular differences in the microsatellite stable phenotype between left‐sided and right‐sided colorectal cancer

Molecular Classification of Patients With Unexplained Hamartomatous and Hyperplastic Polyposis

Unwinding the Heterogeneous Nature of Hamartomatous Polyposis Syndromes

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