Correlation of polyp number and family history of colon cancer with germline MYH mutations.
OBJECTIVE
Affected individuals with biallelic MYH mutations are believed to display multiple adenomatous polyps without evidence of vertical transmission. Our goal was to determine the detection rate of germline MYH mutations in a high-risk gastrointestinal cancer clinic population by using polyp number as a selection criterion.


METHODS
Patients were screened for the 2 most common MYH mutations: Y165C and G382D. The complete MYH coding region was sequenced in cases with a heterozygous mutation.


RESULTS
Among 45 patients with more than 15 adenomatous polyps not diagnosed with familial adenomatous polyposis, 7 (15.6%) had biallelic MYH mutations. When 122 participants from a high-risk gastrointestinal cancer clinic who did not fulfill these criteria were tested, 2 additional patients with biallelic mutations were identified. Both had young-onset colorectal cancer (age, <50 y) with fewer than 15 polyps. Surprisingly, most of the 9 patients with biallelic MYH mutations reported family histories consistent with the hereditary nonpolyposis colorectal cancer syndrome (HNPCC), with 7 cases meeting at least 1 of the Bethesda criteria, 5 cases fulfilling 3 Bethesda criteria, and 2 cases fulfilling the Amsterdam II criteria.


CONCLUSIONS
Most individuals with MYH mutations exhibit multiple adenomatous polyps. However, 22% of cases were missed when this was the sole criterion for germline testing. A significant number reported a strong family history of cancer that was consistent with HNPCC. MYH testing thus can be considered for patients who meet clinical criteria for HNPCC in the absence of DNA mismatch repair gene mutations.
Jo
Won-Seok
WS
Gastrointestinal Unit and Department of Medicine, Cancer Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA.
Bandipalliam
Prathap
P
Shannon
Kristen M
KM
Niendorf
Kristin B
KB
Chan-Smutko
Gayun
G
Hur
Chin
C
Syngal
Sapna
S
Chung
Daniel C
DC
D000328:Adult; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology*; D015179:Colorectal Neoplasms / Q000235:genetics / Q000473:pathology; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics* / Q000473:pathology*; D045647:DNA Glycosylases / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D009154:Mutation
D045647:DNA Glycosylases; C061738:mutY adenine glycosylase