User:13wak/sandbox

Article: Colorectal Cancer

Subsection: Pathogenesis

8. Proposed changed regarding mismatch repair deficiency (insertion into the existing section)

Mismatch repair (MMR) deficient tumours are characterized by deficiency in the MMR proteins – which are typically caused by epigenetic silencing and/or inherited mutations (e.g. Lynch syndrome)^[1]. The mismatch repair system functions to protect the integrity of the genetic material within cells (i.e. it is error detecting and correcting)^[1]. Consequently, MMR deficiency results in an inability to detect and repair genetic damage, allowing for further cancer-causing mutations and enhanced disease progression^[1].

Rationale for proposed change

The above change was included as the current pathogenesis section makes no mention of MMR deficiencies, which are found in 15-18% of CRC tumours ^[2]. Additionally, up to 3% of tumours develop due to Lynch syndrome- an inherited MMR disorder ^[2]. Given the high prevalence of MMR deficiencies in CRC, inclusion in the pathogenesis section seemed appropriate.

9. Proposed change regarding polyp-CRC progression sequence (possible incorporation into the first paragraph of this subsection)

Note- not sure if this should be included in such a manner... open to all suggestions thanks!

*note* Bolded words in the quoted material refer to terms that would be hyperlinked (i.e. attached to a relevant description for laymen reading the article)

“The polyp to cancer progression sequence is the classical model of CRC pathogenesis^[3]. The polyp to cancer sequence describes the phases of transition from benign tumours into CRC over many years^[3]. Central to the polyp to CRC sequence are gene mutations, epigenetic alterations and local inflammatory changes^[3]. The polyp to CRC sequence can be used as an underlying framework to illustrate how specific molecular changes lead to various cancer subtypes^[3].”

Rationale for proposed change

The change shown above was included to provide structure to the pathogenesis section. While the current pathogenesis section is detailed in terms of specific genetic alterations associated with CRC, there is no mention of the classical polyp-CRC progression sequence. Such sequence has been well-described in the CRC literature and could potentially be included in the pathogenesis section. Furthermore, since its original conception, detailed molecular information has been elucidated regarding the various steps of the progression sequence. Further editing of the pathogenesis section could therefore seek to unify the specific genetic mutations with the polyp to CRC progression I included above (as is done in the referenced review article).

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^ ^a ^b ^c Ryan, E.; Sheahan, K.; Creavin, B.; Mohan, H. M.; Winter, D. C. (2017-8). "The current value of determining the mismatch repair status of colorectal cancer: A rationale for routine testing". Critical Reviews in Oncology/Hematology. 116: 38–57. doi:10.1016/j.critrevonc.2017.05.006. ISSN 1879-0461. PMID 28693799. {{cite journal}}: Check date values in: |date= (help)
^ ^a ^b Hissong, Erika; Crowe, Elizabeth P.; Yantiss, Rhonda K.; Chen, Yao-Tseng (2018-11). "Assessing colorectal cancer mismatch repair status in the modern era: a survey of current practices and re-evaluation of the role of microsatellite instability testing". Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc. 31 (11): 1756–1766. doi:10.1038/s41379-018-0094-7. ISSN 1530-0285. PMID 29955148. {{cite journal}}: Check date values in: |date= (help)
^ ^a ^b ^c ^d Grady, William M.; Markowitz, Sanford D. (2015-3). "The molecular pathogenesis of colorectal cancer and its potential application to colorectal cancer screening". Digestive Diseases and Sciences. 60 (3): 762–772. doi:10.1007/s10620-014-3444-4. ISSN 1573-2568. PMC 4779895. PMID 25492499. {{cite journal}}: Check date values in: |date= (help)CS1 maint: PMC format (link)

[:1-1] Ryan, E.; Sheahan, K.; Creavin, B.; Mohan, H. M.; Winter, D. C. (2017-8). "The current value of determining the mismatch repair status of colorectal cancer: A rationale for routine testing". Critical Reviews in Oncology/Hematology. 116: 38–57. doi:10.1016/j.critrevonc.2017.05.006. ISSN 1879-0461. PMID 28693799. {{cite journal}}: Check date values in: |date= (help)

[:2-2] Hissong, Erika; Crowe, Elizabeth P.; Yantiss, Rhonda K.; Chen, Yao-Tseng (2018-11). "Assessing colorectal cancer mismatch repair status in the modern era: a survey of current practices and re-evaluation of the role of microsatellite instability testing". Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc. 31 (11): 1756–1766. doi:10.1038/s41379-018-0094-7. ISSN 1530-0285. PMID 29955148. {{cite journal}}: Check date values in: |date= (help)

[:0-3] Grady, William M.; Markowitz, Sanford D. (2015-3). "The molecular pathogenesis of colorectal cancer and its potential application to colorectal cancer screening". Digestive Diseases and Sciences. 60 (3): 762–772. doi:10.1007/s10620-014-3444-4. ISSN 1573-2568. PMC 4779895. PMID 25492499. {{cite journal}}: Check date values in: |date= (help)CS1 maint: PMC format (link)

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