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Journals / Fırat Üniversitesi Sağlık Bilimleri Tıp Dergisi / 2019 / Cilt: 33 - Sayı: 2

Investigation of APC Gene Mutations in Attenuated Familial Adenomatous Polyposis Coli Cases in Elazığ Region

Elazığ Bölgesinde Attenue Familyal Adenomatöz Poliposis coli (AFAP) Olgularında APC Gen Mutasyonlarının Araştırılması

İbrahim Halil BAHCECİOĞLU
Mehmet YALNIZ
Nurettin TUNÇ
Şenel Sencer TEKTAŞ
Semih DALKILIÇ
Lütfiye DALKILIÇ
Abdurrahman ŞAHİN
Pages
77–81
Publication Date
2022-10-18
DOI
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AI Summary & Key Takeaways

AI Insight
⚡ TL;DR(Too Long; Didn't Read)

Thus, further investigations are required.

📌 3 Key Takeaways

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Objective & Hypothesis:Objective: Colorectal cancers (CRCs) are represent familial characteristics at a rate of 1% and are called familial adenomatous polyposis (FAP) syndrome.
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Key Findings & Data:Mutations responsible for FAP development in order of frequency are seen in the APC gene, MUTYH gene, and POLD1 and POLE genes.
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Conclusion & Impact:Thus, further investigations are required.
🔬Design:Research Article
📍Scope:Comprehensive Sample
⚙️Variables:Domain Parameters

Abstract

Objective: Colorectal cancers (CRCs) are represent familial characteristics at a rate of 1% and are called familial adenomatous polyposis (FAP) syndrome. Mutations responsible for FAP development in order of frequency are seen in the APC gene, MUTYH gene, and POLD1 and POLE genes. We investigated our patients for possible mutations in the APC gene. Materials and Methods: From the isolated DNA samples, 1st ,2nd ,3rd ,4th ,5th ,9th exons and 1000 bp on the 3´ end of the 15th exon of APC, which were determined to have the highest frequency of mutations and polymorphisms that are related to AFP were sequenced by dideoxynucleotide Sanger method and evaluated for genetic variations. Results: A total of 30 patients, 21 males (70%) and 9 females (30%) were included in the study. The mean age of the patients was 43.8 ± 13.0 years. The earliest polyp development age was 20 and early CRC development age was 40 in the families of the patients participated this study. In addition eighteen of the participants (60%) had a history of CRC in their family. No mutation was observed on the studied APC exons in DNA samples obtained from 30 individuals. Conclusion: APC gene mutations were not detected in our patients. In these patients, other genes that may cause attenuated FAP syndrome, the MUTYH gene, and the POLD1 and POLE genes, should be further studied in order to determine the gene or genes that causes the FAP syndrome. Thus, further investigations are required.

Özet

Amaç: Kolorektal kanserlerin (KRK) %1´i ailesel özellik göstermekte ve bunlar familyaladenomatöz polipozis (FAP) sendromu olarak adlandırılmaktadır. FAP gelişiminden sorumlumutasyonlar sıklık sırasına göre APC, MUTYH ve POLD1 ile POLE genlerinde görülür. Yapılan buçalışmada, kolonoskopik işlemlerde 10 veya üzeri polip (10 polip ile 100 polip arası) saptanan veailesinde polipozis koli veya KRK öyküsü olan hastaları attenuated FAP olarak sınıflandırarak, buhastalarda FAP patogenezinde en etkili gen olan APC genindeki olası mutasyonların etkisininaraştırılması amaçlandı.Gereç ve Yöntem: Hastalardan 2 mL, (EDTA´lı Hemogram tüpüne) kan örneği alındı. İzole edilenDNA örneklerinde APC geninin AFP ile ilgili mutasyon ve polimorfizimleri en çok sıklıktabulundurduğu belirlenen 1,2,3,4,5,9. eksonları ve 15. eksonun 3' son kısmında 1000 baz çiftlikkısmı dideoksinükleotid (Sanger) yöntemi ile sekanslanarak genetik varyasyonlar açısındandeğerlendirildi.Bulgular: Çalışmaya 21´i (%70) erkek ve 9´u (%30) kadın toplam 30 hasta alındı. Hastaların yaşortalaması 43.8±13.0 yıldı. Çalışmaya katılan hastaların ailelerinde en erken polip görülme yaşı 20,en erken KRK gelişim yaşı ise 40 olarak bulundu. Çalışmaya katılanların 18´inde (%60) ailede KRKöyküsü mevcuttu. Çalışmaya katılan 30 bireyin DNA örneklerinde, çalışılan APC genininmutasyonlarının hiç birisine rastlanmadı.Sonuç: Attenuted FAP hastalarımızda APC gen mutasyonları saptanmadı. Bu hastalarda,attenuated FAP sendromuna yol açan diğer genler olan MUTYH geni ile POLD1 ve POLE genleriçalışılarak, FAP sendromuna neden olan genin saptanması gerekmektedir ve bu noktada ileriçalışmalara gereksinim vardır.

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Cite This Article

BAHCECİOĞLU, İ. H., YALNIZ, M., TUNÇ, N., TEKTAŞ, Ş. S., DALKILIÇ, S., DALKILIÇ, L., ŞAHİN, A. (2022). Investigation of APC Gene Mutations in Attenuated Familial Adenomatous Polyposis Coli Cases in Elazığ Region. Fırat Üniversitesi Sağlık Bilimleri Tıp Dergisi, Cilt: 33 - Sayı: 2, 77–81. https://ajindex.com/articles/514507

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References (10)

  1. Brody H. Colorectal cancer. Nature 2015; Vol. 521. Issue 7551. Supplement Nature Outlook. Rustgi AK. The genetics of hereditary colon cancer. Genes Dev 2007; 21: 2525-2538.
  2. Huiying MA., Lodewijk AAB., Offerhaus GJA., Giardiello FM., De leng WJW., and Montgomery EA. Pathology and genetics of hereditary colorectal cancer. Pathology 2018; 50: 49–59.
  3. Johns LE, Houlston RS. A systematic review and metaanalysis of familial colorectal cancer risk. Am J Gastroenterol 2001; 96:2992-3003.
  4. Bisgaard ML, Fenger K, Bulow S, Niebuhr E, Mohr J: Familial adenomatous polyposis (FAP): frequency, penetrance, and mutation rate. Hum Mutat 1994; 3:121- 125. Scheuner MT, McNeel TS, Freedman AN: Population prevalence of familial cancer and common hereditary cancer syndromes. The 2005 California Health Interview Survey. Genet Med 2010; 12(11):726-735.
  5. Lucci-Cordisco E, Risio M, Venesio T, Genuardi M: The growing complexity of the intestinal polyposis syndromes. Am J Med Genet A 2013; 161A(11):2777-2787.
  6. Burt RW, Leppert MF, Slattery ML, Samowitz WS, Spirio LN, Kerber RA. et al: Genetic testing and phenotype in a large kindred with attenuated familial adenomatous polyposis. Gastroenterology 2004; 127(2):444-451.
  7. Nieuwenhuis MH, Vasen HF: Correlations between mutation site in APC and phenotype of familial adenomatous polyposis (FAP): a review of the literature. Crit Rev Oncol Hematol 2007; 61(2):153-161.
  8. Ibrahim A, Barnes DR, Dunlop J, Barrowdale D, Antoniou AC, Berg JN: Attenuated familial adenomatous polyposis manifests as autosomal dominant late-onset colorectal cancer. Eur J Hum Genet 2014; 22(11):1330-1333.
  9. Syngal S, Brand RE, Church JM, Giardiello FM, Hampel HL, Burt RW, American College of G: ACG clinical guideline: Genetic testing and management of hereditary gastrointestinal cancer syndromes. Am J Gastroenterol 2015; 110(2):223-262. Jasperson KW: Genetic testing by cancer site: colon (polyposis syndromes). Cancer J 2012; 18(4):328-333.
  10. Palles, C., Cazier, JB., Howarth, KM., Domingo, E., Angela M. Jones, AM. et.al. Germline mutations in the proof-reading domains of POLE and POLD1 predispose to colorectal adenomas and carcinomas. Nat Genet. 2013; 45(2): 136–144. Torrezan GT, da Silva FC, Santos EM, Krepischi AC, Achatz MI, Aguiar S Jr. et.al. Mutational spectrum of the APC and MUTYH genes and genotype-phenotype correlations in Brazilian FAP, AFAP, and MAP patients. Orphanet J Rare Dis. 2013; 5: 8:54. de Leon MP, Urso ED, Pucciarelli S, Agostini M, Nitti D, Roncucci L. et.al. C