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J Med Oncl Ther 2017 | Volume 2 Issue 4
Oncology and Biomarkers Summit
November 27-28, 2017 | Atlanta, USA
Annual Congress on
Statement of the Problem:
Familial adenomatous polyposis
(FAP) is an autosomal dominant inherited disease mainly
caused bymutations of the adenomatous polyposis coli (APC)
gene with almost complete penetrance. These colorectal
polyps are precancerous lesions that will inevitable develop
into colorectal cancer at the median age of 40-year old if
total proctocolectomy is not performed. So, identification of
APC germline mutations has great implications for genetic
counseling and management of FAP patients.
Methodology & Theoretical Orientation:
In this study, we
screened APC germline mutations in Chinese FAP patients,
to find novel mutations and the APC gene germline
mutation characteristics of Chinese FAP patients. The FAP
patients were diagnosed by clinical manifestations, family
histories, endoscope and biopsy. Then patients peripheral
blood samples were collected, afterwards, genomic DNA
was extracted. The mutation analysis of the APC gene was
conducted by direct DNA sequencing for micromutations
and MLPA for large duplications and/or deletions.
Findings:
We found 6 micromutations out of 14 FAP
pedigrees, while there were no large duplications and/or
deletions found. These germline mutations are c.5432C>T
(p. Ser1811Leu), two c.3926_3930delAAAAG (p.Glu1309AspfsX4),
c.3921_3924delAAAA (p.Ile1307MetfsX13), c.3184_3187delCAAA
(p.Gln1061AspfsX59) and c.4127_4126delAT (p.Tyr1376LysfsX9),
respectively and all deletion mutations resulted in a premature
stop codon. At the same time, we found c.3921_3924delAAAA
and two c.3926_3930delAAAAG are in AAAAG short tandem
repeats, c3184_3187delCAAA is in the CAAA interrupted direct
repeats and c4127_4128 del AT is in the 5’-CCTGAACA-3’,
3’-ACAAGTCC-5 palindromes (inverted repeats) of the APC
gene. Furthermore, deletion mutations are mostly located at
codon 1309.
Conclusion & Significance:
Though there were no novel
mutations found as the pathogenic gene of FAP in this study,
we found nucleotide sequence containing short tandem
repeats and palindromes (inverted repeats), especially the
5 bp base deletion at codon 1309, are mutations in high
incidence area in APC gene.
e:
chensenqing2008@126.comAnalysis of small fragment deletions of the APC gene in Chinese patients with familial adenomatous
polyposis
Senqing Chen
Jiangsu Institute of Cancer Research, China