Mosaicism in Patients With Colorectal Cancer or Polyposis Syndromes: A Systematic Review

Jansen, Anne M.L.; Goel, Ajay

doi:10.1016/j.cgh.2020.02.049

Cited by 27 publications

(20 citation statements)

References 94 publications

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“…Anyway, analysis pipelines dedicated to mosaic detection in NGS data may be useful for a few patients with no history of cancer in the ascendants, at least to exclude somatic mosaicism. Alternatively, MMR analysis in the tumor and subsequent screen for the pathogenic variants in nontumoral tissues with highly sensitive technics might be the strategy to exclude low-level mosaicism and mosaicism not detectable in lymphocyte DNA [ 207 ].…”

Section: Diagnosis Of Lynch Syndromementioning

confidence: 99%

Diagnosis of Lynch Syndrome and Strategies to Distinguish Lynch-Related Tumors from Sporadic MSI/dMMR Tumors

Leclerc

Vermaut²,

Buisine

2021

Cancers

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Microsatellite instability (MSI) is a hallmark of Lynch syndrome (LS)-related tumors but is not specific to it, as approximately 80% of MSI/mismatch repair-deficient (dMMR) tumors are sporadic. Methods leading to the diagnosis of LS have considerably evolved in recent years and so have tumoral tests for LS screening and for the discrimination of LS-related to MSI-sporadic tumors. In this review, we address the hallmarks of LS, including the clinical, histopathological, and molecular features. We present recent advances in diagnostic and screening strategies to identify LS patients. We also discuss the pitfalls associated with the current strategies, which should be taken into account to improve the diagnosis of LS and avoid inappropriate clinical management.

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Section: Diagnosis Of Lynch Syndromementioning

confidence: 99%

Diagnosis of Lynch Syndrome and Strategies to Distinguish Lynch-Related Tumors from Sporadic MSI/dMMR Tumors

Leclerc

Vermaut²,

Buisine

2021

Cancers

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“…Mosaicism might remain undetectable or be overlooked if the molecular analysis is limited to blood, even when sensitive techniques are applied, due to very low or even absent presentation of the mutated allele [ 23 , 27 ]. Peripheral blood cells arise from the mesoderm, and when the variant occurs after mesoderm and endoderm specification (early postzygotic mutation), the mosaicism is likely restricted to the colon and is difficult to detect the variant in leukocyte DNA [ 23 , 27 , 32 , 33 ]. In a previous study, it was recommended to test at least two or more adenomas to detect mosaic variants [ 27 ].…”

Section: Resultsmentioning

confidence: 99%

“…A recent systematic review of current APC mosaicism studies recommends testing adenomas from the polyposis patients without APC germline variant to allow the detection of low allele frequency mosaicism as well as mosaicism confined to colon [ 33 ]. Consequently, in our study, APC mosaic variants confined to the colon could have been missed because we could not screen the DNA from the adenomas of the patients.…”

Section: Resultsmentioning

confidence: 99%

Use of sanger and next-generation sequencing to screen for mosaic and intronic APC variants in unexplained colorectal polyposis patients

et al. 2021

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In addition to classic germline APC gene variants, APC mosaicism and deep intronic germline APC variants have also been reported to be causes of adenomatous polyposis. In this study, we investigated 80 unexplained colorectal polyposis patients without germline pathogenic variants in known polyposis predisposing genes to detect mosaic and deep intronic APC variants. All patients developed more than 50 colorectal polyps, with adenomas being predominantly observed. To detect APC mosaicism, we performed next-generation sequencing (NGS) in leukocyte DNA. Furthermore, using Sanger sequencing, the cohort was screened for the following previously reported deep intronic pathogenic germline APC variants: c.1408 + 731C > T, p.(Gly471Serfs*55), c.1408 + 735A > T, p.(Gly471Serfs*55), c.1408 + 729A > G, p.(Gly471Serfs*55) and c.532-941G > A, p.(Phe178Argfs*22). We did not detect mosaic or intronic APC variants in the screened unexplained colorectal polyposis patients. The results of this study indicate that the deep intronic APC variants investigated in this study are not a cause of colorectal polyposis in this Dutch population. In addition, NGS did not detect any further mosaic variants in our cohort.

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“…A single extra tooth is the most common manifestation; three or more supernumerary teeth are found in only 1% of cases [88]. The prevalence of supernumerary teeth in patients with FAP ranges from 11% to 27% [8].…”

Section: Dental Abnormalitiesmentioning

confidence: 99%

“…Genetic variants that arise post-zygotically are not present in all body cells, posing a unique diagnostic challenge. Mosaicism in CRC susceptibility genes, mainly APC, has been reported in a significant portion of patients with undiagnosed polyposis [6][7][8]. In addition to the milder clinical phenotype, which may be interpreted as a "normal variation", cases of mosaicism are likely to be underdiagnosed because of the limited sensitivity of conventional molecular diagnostic techniques, insufficient material used for testing, and the false assumption that when a family history is absent the patient's cancer is sporadic [6].…”

Section: Introductionmentioning

confidence: 99%

Nonmalignant Features Associated with Inherited Colorectal Cancer Syndromes-Clues for Diagnosis

Haimov

Lieberman

Castellví–Bel

et al. 2022

Cancers

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Genetic diagnosis of affected individuals and predictive testing of their at-risk relatives, combined with intensive cancer surveillance, has an enormous cancer-preventive potential in these families. A lack of awareness may be part of the reason why the underlying germline cause remains unexplained in a large proportion of patients with CRC. Various extracolonic features, mainly dermatologic, ophthalmic, dental, endocrine, vascular, and reproductive manifestations occur in many of the cancer predisposition syndromes associated with CRC and polyposis. Some are mediated via the WNT, TGF-β, or mTOR pathways. However the pathogenesis of most features is still obscure. Here we review the extracolonic features of the main syndromes, the existing information regarding their prevalence, and the pathways involved in their pathogenesis. This knowledge could be useful for care managers from different professional disciplines, and used to raise awareness, enable diagnosis, and assist in the process of genetic testing and interpretation.

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Mosaicism in Patients With Colorectal Cancer or Polyposis Syndromes: A Systematic Review

Cited by 27 publications

References 94 publications

Diagnosis of Lynch Syndrome and Strategies to Distinguish Lynch-Related Tumors from Sporadic MSI/dMMR Tumors

Diagnosis of Lynch Syndrome and Strategies to Distinguish Lynch-Related Tumors from Sporadic MSI/dMMR Tumors

Use of sanger and next-generation sequencing to screen for mosaic and intronic APC variants in unexplained colorectal polyposis patients

Nonmalignant Features Associated with Inherited Colorectal Cancer Syndromes-Clues for Diagnosis

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