Distinct Patterns of Somatic Mosaicism in the APC Gene in Neoplasms From Patients With Unexplained Adenomatous Polyposis.
We investigated the presence and patterns of mosaicism in the APC gene in patients with colon neoplasms not associated with any other genetic variants; we performed deep sequence analysis of APC in at least 2 adenomas or carcinomas per patient. We identified mosaic variants in APC in adenomas from 9 of the 18 patients with 21 to approximately 100 adenomas. Mosaic variants of APC were variably detected in leukocyte DNA and/or non-neoplastic intestinal mucosa of these patients. In a comprehensive sequence analysis of 1 patient, we found no evidence for mosaicism in APC in non-neoplastic intestinal mucosa. One patient was found to carry a mosaic c.4666dupA APC variant in only 10 of 16 adenomas, indicating the importance of screening 2 or more adenomas for genetic variants.
Department of Pathology, Leiden University Medical Centre, Leiden, The Netherlands; Department of Human Genetics, Leiden University Medical Centre, Leiden, The Netherlands.
Anne M L
AM
Jansen
Department of Pathology, Leiden University Medical Centre, Leiden, The Netherlands.
Stijn
S
Crobach
Department of Pathology, Erasmus MC Cancer Institute, University Medical Centre Rotterdam, The Netherlands.
Willemina R R
WR
Geurts-Giele
Department of Pathology, Leiden University Medical Centre, Leiden, The Netherlands.
Brendy E W M
BE
van den Akker
Department of Pathology, Leiden University Medical Centre, Leiden, The Netherlands.
Marina Ventayol
MV
Garcia
Department of Pathology, Leiden University Medical Centre, Leiden, The Netherlands.
Dina
D
Ruano
Department of Clinical Genetics, Leiden University Medical Centre, Leiden, The Netherlands.
Maartje
M
Nielsen
Department of Clinical Genetics, Leiden University Medical Centre, Leiden, The Netherlands.
Carli M J
CM
Tops
Department of Human Genetics, Leiden University Medical Centre, Leiden, The Netherlands; Department of Clinical Genetics, Leiden University Medical Centre, Leiden, The Netherlands.
Juul T
JT
Wijnen
Department of Clinical Genetics, Leiden University Medical Centre, Leiden, The Netherlands.
Frederik J
FJ
Hes
Department of Pathology, Leiden University Medical Centre, Leiden, The Netherlands.
Tom
T
van Wezel
Department of Pathology, Erasmus MC Cancer Institute, University Medical Centre Rotterdam, The Netherlands.
Winand N M
WN
Dinjens
Department of Pathology, Leiden University Medical Centre, Leiden, The Netherlands. Electronic address: j.morreau@lumc.nl.
Hans
H
Morreau
D000236:Adenoma / Q000235:genetics*; D011125:Adenomatous Polyposis Coli / Q000235:genetics*; D000328:Adult; D000368:Aged; D002277:Carcinoma / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics*; D005260:Female; D017491:Genes, APC; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D008875:Middle Aged; D009030:Mosaicism; D009378:Neoplasms, Multiple Primary / Q000235:genetics*; D017422:Sequence Analysis, DNA; D060449:Wnt Signaling Pathway
Wnt signaling; colorectal carcinogenesis; mutation; unexplained polyposis