MOLECULAR CHARACTERIZATION OF FAMILIAL ADENOMATOUS POLYPOSIS IN THE REPUBLIC OF MACEDONIA
Stefanovska A-M1, Josifovski T2, Panovski M2, Jasar D3, Zografski G3, Efremov GD1, Dimovski AJ1,4,*
*Corresponding Author: Professor Dr. Aleksandar J. Dimovski, Faculty of Pharmacy, Vodnjanska 17, 1000 Skopje, Republic of Macedonia; Tel: +389-2-311-9694; Fax: +389-2-312-3054; E-mail: adimovski@baba.ff.ukim.edu.mk
page: 33

INTRODUCTION

It is well known that colorectal tumours progress through a series of clinical and histopathological stages, ranging from aberrant crypt foci, through adenomatous polyps to carcinomas. The adenomatous polyp is a prototype of a preneoplastic lesion and a biomarker for increased risk of development of colorectal cancer. It is generally believed that the molecular events responsible for its development can be used for early detection, improved management and better prognosis of colorectal cancer [1]. Development of colorectal polyps is age-related, such polyps occurring in approximately 20% of individuals older than 70 years of age. There are several inherited conditions that are characterized by a predisposition for the development of numerous colorectal polyps at an early age. The best defined of these is the familial adenomatous polyposis (FAP) syndrome, which is a dominantly inherited predisposition to colorectal tumours that accounts for up to 1% of cancers of the large bowel [2]. In its classical form, FAP is characterized by hundreds to thousands of adenomatous polyps throughout the colorectum, early onset of colorectal carcinoma, and frequent extracolonic features such as adenomatous polyps of the upper gastrointestinal tract, soft tissue and skeletal tumours, ocular changes, and brain and thyroid malignancies [3 The molecular basis of FAP is germ-line mutational inactivation of the adenomatous polyposis coli (APC) gene. Most of the defects in classical FAP syndrome are point mutations or small deletions/insertions clustered between codons 200 and 1600 that result in a truncated APC protein. Large deletions of the APC gene are present in approximately 10% of patients [4], while in 20-50% of patients, the molecular defect in the gene could not be detected [5]. Although the familial component is a hallmark of this disease, up to one-third of patients have a de novo mutation which further complicates the genetic analysis and management. A phenotypic variant of the syndrome, named attenuated FAP (AAPC) is characterized by the presence of less than 100 adenomas in the colorectum [6]. Mutations in the APC gene also occur in these patients, and are clustered in the 5’ and 3’ ends of the gene and in the alternatively spliced portion of exon 9 [7].

      Several investigators have reported that the AAPC can be clinically similar to the hereditary non polyposis colorectal cancer (HNPCC) syndrome which results from mutations in genes for the mismatch repair (MMR) complex. Patients with HNPCC have a smaller number of adenomas (<10) and are at high risk for the development of colorectal carcinoma at an early age [8]. Both adenomas and carcinomas from these patients exhibit an instability in the microsatellite repeats, the so-called microsatellite instability (MSI) phenotype, that is due to the underlying genetic defect [9].

      A new clinical entity has recently been proposed, i.e., “multiple adenoma patients” [3]. This refers to patients with an AAPC-like phenotype with 3-99 polyps in the colorectum, no family history of polyposis and no detectable mutation in the APC and MMR genes [3]. This condition may be due to mutations in the APC2, MYH gene or to specific external influences [3,10,11].

       The aim of this study was to evaluate the molecular profile of patients with histopathologically confirmed multiple colonic adenomatous polyposis from the Republic of Macedonia.




Number 21
VOL. 21 (1), 2018
Number 21
VOL. 21, 2018 Accepted articles (Accepted, unedited articles, published online and can be cited. The final edited and printed version of the manuscript will appear in future)
Number 21
VOL. 21, 2018 Supplement
Number 20
VOL. 20 (2), 2017
Number 20
VOL. 20 (1), 2017
Number 19
VOL. 19 (2), 2016
Number 19
VOL. 19 (1), 2016
Number 18
VOL. 18 (2), 2015
Number 18
VOL. 18 (1), 2015
Number 17
VOL. 17 (2), 2014
Number 17
VOL. 17 (1), 2014
Number 16
VOL. 16 (2), 2013
Number 16
VOL. 16 (1), 2013
Number 15
VOL. 15 (2), 2012
Number 15
VOL. 15, 2012 Supplement
Number 15
Vol. 15 (1), 2012
Number 14
14 - Vol. 14 (2), 2011
Number 14
The 9th Balkan Congress of Medical Genetics
Number 14
14 - Vol. 14 (1), 2011
Number 13
Vol. 13 (2), 2010
Number 13
Vol.13 (1), 2010
Number 12
Vol.12 (2), 2009
Number 12
Vol.12 (1), 2009
Number 11
Vol.11 (2),2008
Number 11
Vol.11 (1),2008
Number 10
Vol.10 (2), 2007
Number 10
10 (1),2007
Number 9
1&2, 2006
Number 9
3&4, 2006
Number 8
1&2, 2005
Number 8
3&4, 2004
Number 7
1&2, 2004
Number 6
3&4, 2003
Number 6
1&2, 2003
Number 5
3&4, 2002
Number 5
1&2, 2002
Number 4
Vol.3 (4), 2000
Number 4
Vol.2 (4), 1999
Number 4
Vol.1 (4), 1998
Number 4
3&4, 2001
Number 4
1&2, 2001
Number 3
Vol.3 (3), 2000
Number 3
Vol.2 (3), 1999
Number 3
Vol.1 (3), 1998
Number 2
Vol.3(2), 2000
Number 2
Vol.1 (2), 1998
Number 2
Vol.2 (2), 1999
Number 1
Vol.3 (1), 2000
Number 1
Vol.2 (1), 1999
Number 1
Vol.1 (1), 1998

 

 


 About the journal ::: Editorial ::: Subscription ::: Information for authors ::: Contact
 Copyright © Balkan Journal of Medical Genetics 2006