GLORIA

GEOMAR Library Ocean Research Information Access

X

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Online Resource
    Online Resource
    Methylated SEPTIN9 plasma test for colorectal cancer detection may be applicable to Lynch syndrome
    BMJ ; 2019
    In:  BMJ Open Gastroenterology Vol. 6, No. 1 ( 2019-05), p. e000299-
    Details
    In: BMJ Open Gastroenterology, BMJ, Vol. 6, No. 1 ( 2019-05), p. e000299-
    Abstract: The plasma-based methylated SEPTIN9 (mSEPT9) is a colorectal cancer (CRC) screening test for adults aged 50–75 years who are at average risk for CRC and have refused colonoscopy or faecal-based screening tests. The applicability of mSEPT9 for high-risk persons with Lynch syndrome (LS), the most common hereditary CRC condition, has not been assessed. This study sought preliminary evidence for the utility of mSEPT9 for CRC detection in LS. Design Firstly, SEPT9 methylation was measured in LS-associated CRC, advanced adenoma, and subject-matched normal colorectal mucosa tissues by pyrosequencing. Secondly, to detect mSEPT9 as circulating tumor DNA, the plasma-based mSEPT9 test was retrospectively evaluated in LS subjects using the Epi proColon 2.0 CE assay adapted for 1mL plasma using the “1/1 algorithm”. LS case groups included 20 peri-surgical cases with acolonoscopy-based diagnosis of CRC (stages I-IV), 13 post-surgical metastatic CRC, and 17 pre-diagnosis cases. The control group comprised 31 cancer-free LS subjects. Results Differential hypermethylation was found in 97.3% (36/37) of primary CRC and 90.0% (18/20) of advanced adenomas, showing LS-associated neoplasia frequently produce the mSEPT9 biomarker. Sensitivity of plasma mSEPT9 to detect CRC was 70.0% (95% CI, 48%-88%)in cases with a colonoscopy-based CRC diagnosis and 92.3% (95% CI, 64%-100%) inpost-surgical metastatic cases. In pre-diagnosis cases, plasma mSEPT9 was detected within two months prior to colonoscopy-based CRC diagnosis in 3/5 cases. Specificity in controls was 100% (95% CI 89%-100%). Conclusion These preliminary findings suggest mSEPT9 may demonstrate similar diagnostic performance characteristics in LS as in the average-risk population, warranting a well-powered prospective case–control study.
    Type of Medium: Online Resource
    ISSN: 2054-4774
    URL: Article
    DOI: 10.1136/bmjgast-2019-000299
    Language: English
    Publisher: BMJ
    Publication Date: 2019
    detail.hit.zdb_id: 2884818-4
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 2
    Online Resource
    Online Resource
    Genetic architectures of proximal and distal colorectal cancer are partly distinct
    BMJ ; 2021
    In:  Gut Vol. 70, No. 7 ( 2021-07), p. 1325-1334
    Details
    In: Gut, BMJ, Vol. 70, No. 7 ( 2021-07), p. 1325-1334
    Abstract: An understanding of the etiologic heterogeneity of colorectal cancer (CRC) is critical for improving precision prevention, including individualized screening recommendations and the discovery of novel drug targets and repurposable drug candidates for chemoprevention. Known differences in molecular characteristics and environmental risk factors among tumors arising in different locations of the colorectum suggest partly distinct mechanisms of carcinogenesis. The extent to which the contribution of inherited genetic risk factors for CRC differs by anatomical subsite of the primary tumor has not been examined. Design To identify new anatomical subsite-specific risk loci, we performed genome-wide association study (GWAS) meta-analyses including data of 48 214 CRC cases and 64 159 controls of European ancestry. We characterised effect heterogeneity at CRC risk loci using multinomial modelling. Results We identified 13 loci that reached genome-wide significance (p 〈 5×10 −8 ) and that were not reported by previous GWASs for overall CRC risk. Multiple lines of evidence support candidate genes at several of these loci. We detected substantial heterogeneity between anatomical subsites. Just over half (61) of 109 known and new risk variants showed no evidence for heterogeneity. In contrast, 22 variants showed association with distal CRC (including rectal cancer), but no evidence for association or an attenuated association with proximal CRC. For two loci, there was strong evidence for effects confined to proximal colon cancer. Conclusion Genetic architectures of proximal and distal CRC are partly distinct. Studies of risk factors and mechanisms of carcinogenesis, and precision prevention strategies should take into consideration the anatomical subsite of the tumour.
    Type of Medium: Online Resource
    ISSN: 0017-5749 , 1468-3288
    URL: Article
    DOI: 10.1136/gutjnl-2020-321534
    RVK:
    XA 10000
    Language: English
    Publisher: BMJ
    Publication Date: 2021
    detail.hit.zdb_id: 1492637-4
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 3
    Online Resource
    Online Resource
    Clinical characteristics of patients with colorectal cancer with double somatic mismatch repair mutations compared with Lynch syndrome
    BMJ ; 2019
    In:  Journal of Medical Genetics Vol. 56, No. 7 ( 2019-07), p. 462-470
    Details
    In: Journal of Medical Genetics, BMJ, Vol. 56, No. 7 ( 2019-07), p. 462-470
    Abstract: Patients with colorectal cancer (CRC) with mismatch repair-deficient (dMMR) tumours without MLH1 methylation or germline MMR pathogenic variants (PV) were previously thought to have Lynch syndrome (LS). It is now appreciated that they can have double somatic (DS) MMR PVs. We explored the clinical characteristics between patients with DS tumours and LS in two population-based cohorts. Methods We included patients with CRC from Ohio 2013–2016 and Iceland 2000–2009. All had microsatellite instability testing and/or immunohistochemistry (IHC) of MMR proteins, and MLH1 methylation testing when indicated. Germline next-generation sequencing was performed for all with dMMR tumours; tumour sequencing followed for patients with unexplained dMMR. Clinical characteristics of DS patients and patients with LS were compared. Results Of the 232 and 51 patients with non-methylated dMMR tumours in the Ohio and Iceland cohorts, respectively, 57.8% (n=134) and 45.1% (n=23) had LS, 32.8% (n=76) and 31.4% (n=16) had DS PVs, 6% (n=14) and 9.8% (n=5) were unexplained and 4.3% (n=10) and 13.7% (n=7) had incorrect IHC. Age of diagnosis for DS patients was older than patients with LS (p=3.73×10 −4 ) in the two cohorts. Patients with LS were more likely to meet Amsterdam II criteria (OR=15.81, p=8.47×10 −6 ) and have multiple LS-associated tumours (OR=6.67, p=3.31×10 −5 ). Absence of MLH1/PMS2 was predictive of DS PVs; isolated MSH6 and PMS2 absence was predictive of LS in both cohorts. Conclusions Individuals with LS are 15× more likely to meet Amsterdam II criteria and 〉 5× more likely to have multiple cancers as compared with those with DS tumours. Furthermore, isolated loss of MSH6 or PMS2 protein predicts LS.
    Type of Medium: Online Resource
    ISSN: 0022-2593 , 1468-6244
    URL: Article
    DOI: 10.1136/jmedgenet-2018-105698
    RVK:
    WA 15000
    Language: English
    Publisher: BMJ
    Publication Date: 2019
    detail.hit.zdb_id: 2009590-9
    SSG: 12
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 4
    Online Resource
    Online Resource
    Diagnostic criteria for constitutional mismatch repair deficiency (CMMRD): recommendations from the international consensus working group
    BMJ ; 2022
    In:  Journal of Medical Genetics Vol. 59, No. 4 ( 2022-04), p. 318-327
    Details
    In: Journal of Medical Genetics, BMJ, Vol. 59, No. 4 ( 2022-04), p. 318-327
    Abstract: Constitutional mismatch repair deficiency syndrome (CMMRD) is the most aggressive cancer predisposition syndrome associated with multiorgan cancers, often presenting in childhood. There is variability in age and presentation of cancers and benign manifestations mimicking neurofibromatosis type 1. Genetic testing may not be informative and is complicated by pseudogenes associated with the most commonly associated gene, PMS2 . To date, no diagnostic criteria exist. Since surveillance and immune-based therapies are available, establishing a CMMRD diagnosis is key to improve survival. Methods In order to establish a robust diagnostic path, a multidisciplinary international working group, with representation from the two largest consortia (International Replication Repair Deficiency (IRRD) consortium and European Consortium Care for CMMRD (C4CMMRD)), was formed to establish diagnostic criteria based on expertise, literature review and consensus. Results The working group established seven diagnostic criteria for the diagnosis of CMMRD, including four definitive criteria (strong evidence) and three likely diagnostic criteria (moderate evidence). All criteria warrant CMMRD surveillance. The criteria incorporate germline mismatch repair results, ancillary tests and clinical manifestation to determine a diagnosis. Hallmark cancers for CMMRD were defined by the working group after extensive literature review and consultation with the IRRD and C4CMMRD consortia. Conclusions This position paper summarises the evidence and rationale to provide specific guidelines for CMMRD diagnosis, which necessitates appropriate surveillance and treatment.
    Type of Medium: Online Resource
    ISSN: 0022-2593 , 1468-6244
    URL: Article
    DOI: 10.1136/jmedgenet-2020-107627
    RVK:
    WA 15000
    Language: English
    Publisher: BMJ
    Publication Date: 2022
    detail.hit.zdb_id: 2009590-9
    SSG: 12
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...