scholarly journals Mutational Analysis of a Familial Adenomatous Polyposis Pedigree with Bile Duct Polyp Phenotype

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Li-jun Xie ◽  
Dan-dan Ruan ◽  
Jian-hui Zhang ◽  
Yi Li ◽  
Li Chen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Bile Duct ◽  
Familial Adenomatous Polyposis ◽  
Common Bile Duct ◽  
Mutational Analysis ◽  
Stop Codon ◽  
Genetic Linkage Analysis ◽  
Extraintestinal Manifestations ◽  
Adenomatous Polyposis ◽  
Colorectal Cancer Patients

A large number of colorectal cancers have a genetic background in China. However, due to insufficient awareness, the diagnostic rate remains low and merely 5-6% of colorectal cancer patients are diagnosed with hereditary colorectal cancer. Familial adenomatous polyposis (FAP) is an autosomal dominant genetic disease caused by mutations in the adenomatous polyposis coli (APC) gene. Different mutation sites in APC are associated with the severity of FAP, risks of carcinogenesis, and extraintestinal manifestations. We used next-generation sequencing (NGS) and capture techniques to screen suspected mutation points in the proband in this pedigree. Using modified Sanger sequencing, we identified members of the family who were carriers of this variant and whether this segregated well with disease occurrence. FAP family members had multiple adenomatous polyps in their gastrointestinal tracts, some of which developed into cancer with age. Two subjects presented a rare common bile duct polyp phenotype. No extraintestinal manifestations were observed. A heterozygous frameshift mutation in APC exon 16 (NM_000038.6) was observed in the proband and in other patients: c.3260_3261del (p.Leu1087GlnQfs ∗ 31) (rs587782305); the variant call format was CCT/C. Due to the deletion of two bases, a stop codon appeared after 31 amino acids, and the protein was truncated prematurely, which affected the conformation of the protein. Pedigree genetic linkage analysis showed that the clinical phenotype cosegregated with the APC mutation p.L1087fs. This mutation may be the pathogenic in this FAP family and responsible for this rare common bile duct polyp.

A New Germline Stop Codon Mutation in Exon 15 of the APC Gene Predisposing to Familial Adenomatous Polyposis

2013 ◽  
Vol 28 (4) ◽  
pp. 405-408 ◽  
Author(s):  
Laura Schirosi ◽  
Marcello Pellegrino ◽  
Paolo Tarantino ◽  
Salvatore Mauro ◽  
Andrea Tinelli ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Familial Adenomatous Polyposis ◽  
Germline Mutation ◽  
Stop Codon ◽  
Premature Stop Codon ◽  
Colorectal Tumor ◽  
Apc Gene ◽  
Sequencing Analysis ◽  
Adenomatous Polyposis ◽  
Truncated Protein

Familial adenomatous polyposis (FAP) is an autosomal dominant disorder related to germline mutations of the adenomatous polyposis coli ( APC) gene. It is characterized by the detection of numerous adenomatous polyps that, if untreated, develop into colorectal cancer. We studied an Italian family with FAP history and the related colorectal tumor sample of the proband. Sequencing analysis of blood samples revealed the presence of a never-reported germline mutation in the APC gene (exon 15): an heterozygous G deletion at position c.2126 resulting in a premature stop codon (p.Gly721GlufsX6) and in a truncated protein. This mutation was also identified in the colorectal tumor tissue, together with a second known pathogenic heterozygotic somatic mutation, c.4348C>T (p.Arg1450X), which generates a premature truncated protein. The novel identified germline mutation is therefore related to FAP and, in accordance with Knudson's “two hit” hypothesis, can be considered the first event predisposing to the insurgence of colorectal cancer in these patients. The somatic hit inactivating the second allele of the APC gene is located in the mutation cluster region of the gene; this is not a random event since it depends on the position of the germline mutation. The inactivation of APC generates the neoplastic growth advantage to the cell.

Hereditary Colorectal Cancer and Polyposis Syndromes

2021 ◽  
Author(s):  
Jose G. Guillem ◽  
John B Ammori
Keyword(s):  
Colorectal Cancer ◽  
Familial Adenomatous Polyposis ◽  
Lynch Syndrome ◽  
Juvenile Polyposis ◽  
Prophylactic Surgery ◽  
Cancer Type ◽  
Adenomatous Polyposis ◽  
Juvenile Polyposis Syndrome ◽  
Polyposis Syndrome ◽  
Peutz Jeghers Syndrome

The majority of cases of inherited colorectal cancer (CRC) are accounted for by two syndromes: Lynch syndrome and familial adenomatous polyposis (FAP). In the management of FAP, the role of prophylactic surgery is clearly defined, although the optimal procedure for an individual patient depends on a number of factors. In the management of Lynch syndrome, the indications for prophylactic procedures are emerging. The authors address the clinical evaluation, investigation findings, medical and surgical therapy, and extracolonic diseases of FAP, attenuated form of FAP (AFAP), MYH-associated polyposis, Lynch syndrome, familial colorectal cancer type X (FCCTX), hyperplastic polyposis syndrome, Peutz-Jeghers syndrome, and juvenile polyposis syndrome. AFAP has been described that is associated with fewer adenomas and later development of CRC compared with classic FAP. The AFAP phenotype occurs in less than 10% of FAP patients. The clinical criteria for AFAP are no family members with more than 100 adenomas before the age of 30 years and (1) at least two patients with 10 to 99 adenomas at age over 30 years or (2) one patient with 10 to 99 adenomas at age over 30 years and a first-degree relative with CRC with few adenomas. Given that polyposis has a later onset and the risk of CRC is less well established in AFAP, some authors question whether prophylactic colectomy is necessary in all AFAP patients. This review contains 26 tables and 173 references Keywords: Colorectal cancer, Lynch syndrome, hyperplastic polyp, Peutz-Jeghers syndrome, juvenile polyposis syndrome, familial adenomatous polyposis

What's New in Hereditary Colorectal Cancer?

2005 ◽  
Vol 129 (11) ◽  
pp. 1380-1384 ◽  
Author(s):  
Jeremy R. Jass
Keyword(s):  
Colorectal Cancer ◽  
Familial Adenomatous Polyposis ◽  
Hereditary Nonpolyposis Colorectal Cancer ◽  
Practical Significance ◽  
Adenomatous Polyposis ◽  
Repair Gene ◽  
Attenuated Familial Adenomatous Polyposis ◽  
Dna Repair Gene ◽  
Hereditary Nonpolyposis ◽  
Revised Bethesda Guidelines

Abstract Precancerous polyposes other than classic familial adenomatous polyposis and the condition hereditary nonpolyposis colorectal cancer, or Lynch syndrome, continue to present major diagnostic challenges for the anatomic pathologist. This editorial highlights the practical significance of novel insights and clinical guidelines in the recent literature, as well as in 4 contributions to this edition of the Archives of Pathology & Laboratory Medicine. The first section will address attenuated familial adenomatous polyposis and a newly recognized type of autosomal-recessive adenomatous polyposis associated with the DNA repair gene MYH. The remainder of the editorial discusses the role of the revised Bethesda guidelines in the diagnosis of hereditary nonpolyposis colorectal cancer and concludes with the recently identified serrated pathway syndrome.

Colorectal cancer in two pre-teenage siblings with familial adenomatous polyposis

2005 ◽  
Vol 164 (5) ◽  
pp. 306-310 ◽  
Author(s):  
Silvija Jerkic ◽  
Hendrik Rosewich ◽  
Jens-Gerd Scharf ◽  
Christina Perske ◽  
Laszlo F�zesi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Familial Adenomatous Polyposis ◽  
Adenomatous Polyposis
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