APC gene analysis in familial adenomatosis polyposis: 3 new mutations in Turkish population

INTRODUCTION: Colorectal cancer (CRC) is among the three most common types of cancer worldwide. Less than 10% of CRC patients are associated with germline mutations that form hereditary CRC syndromes. APC gene mutations in the familial adenomatous polyposis (FAP) leading to the adenomatous polyp are at the top of these diseases. In our study, we aimed to determine the type and structure of APC mutations observed in Turkish society.

METHODS: 24 patients applied to our clinic for FAP. Peripheral blood sample was collected from these patients and DNA isolated. Sequencing was performed with the new generation sequencing method in the Illumina MiSeq system. Data analyzes were performed on QIAGEN Clinical Insight (QCITM).

RESULTS: Pathogenic mutation was detected in 6 (25%) of 24 patients, while two different pathogenic mutations (c.3183_3187delACAAA and c.163C> T) were detected in one patient. The c.2309C> G (p.S770*) mutation was detected in two siblings. In addition, c.4393_4394delCC (p.S1465fs*3), c.4405_4406dupCA (p.Q1469fs*5), c.4312delA (p.T1438fs*35), c.3927_3931delAAAGA (p.E1309fs*4) mutations were detected.

DISCUSSION AND CONCLUSION: As the main causes of FAP, mutations in the APC gene have been reported most frequently. There are more than 2000 mutations in the literature. In our study, 25% pathogenic mutations were detected in accordance with the literature. Of these mutations, c.163C> T (p.Q55*) in exon 1 and c.4312delA (p.T1438fs*35) in exon 16, are reported for the first time. With the reporting of new mutations, it is seen that especially the 1st and 14th exons besides the 16th exon can take place and the structure of the gene can be better understood with new mutations.

Familyal Adenomatozis Polipoziste APC geni analizi: Türk toplumunda 3 yeni mutasyon

GÝRÝÞ ve AMAÇ: Kolorektal kanser (KRK), tüm dünyada en sýk görülen üç kanser tipi arasýndadýr. KRK hastalarýnýn %10’undan azý herediter KRK sendromlarýný oluþturan germline mutasyonlar ile iliþkilidir. Bu hastalýklarýn baþýnda adenomatöz poliple giden ailesel adenomatöz polipoziste (FAP) APC geni mutasyonlarý gelir. Çalýþmamýzda Türk toplumunda gözlenen APC mutasyonlarýnýn tipini ve yapýsýný belirlemeyi amaçladýk.
YÖNTEM ve GEREÇLER: Kliniðimize FAP nedeniyle 24 hasta baþvurdu. Bu hastalardan çalýþma için periferik kan örneði alýnýp, DNA izolasyonu yapýldý. Sekanslama iþlemi Illumina MiSeq sisteminde yeni nesil dizileme yöntemi ile gerçekleþtirildi. Veri analizleri QIAGEN Clinical Insight (QCITM) üzerinde gerçekleþtirildi.
BULGULAR: 24 hastanýn 6’sýnda (%25) patojenik mutasyon tespit edilirken, bir hastada iki farklý patojenik mutasyon (c.3183_3187delACAAA ve c.163C>T) tespit edildi. c.2309C>G(p.S770*) mutasyonu iki kardeþte tespit edildi. Bunlar dýþýnda c.4393_4394delCC(p.S1465fs*3), c.4405_4406dupCA(p.Q1469fs*5), c.4312delA(p.T1438fs*35), c.3927_3931delAAAGA(p.E1309fs*4) mutasyonlarý tespit edildi.
TARTIÞMA ve SONUÇ: FAP’ýn nedenlerinden olarak en sýk APC genindeki mutasyonlar bildirilmiþtir. Literatürde 2000’den fazla mutasyon yer almaktadýr. Bizim çalýþmamýzda literatür ile uyumlu olarak %25 patojenik mutasyon saptandý. Bu mutasyonlardan 1. ekzondaki c.163C>T (p.Q55*) ile 16. Ekzondaki c.4312delA(p.T1438fs*35), c.4405_4406dupCA (p.Q1469fs*5), ilk defa bizim çalýþmamýzda bildirilmektedir. Yeni mutasyonlarýn bildirilmesi ile genin özellikle 16. ekzon dýþýnda 1. ve 14. ekzonlarýnýn da önemli yer alabileceðini ve yeni mutasyonlarla genin yapýsýnýn daha iyi anlaþýlabileceði görülmektedir.