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Microsatellite instability in saliva from patients with hereditary non-polyposis colon cancer and siblings carrying germline mismatch repair gene mutations.
Ann Clin Lab Sci. 2011 Fall; 41(4):321-30.AC

Abstract

Microsatellites are short tandem repeats of deoxyribonucleic acid (DNA) sequences which are distributed throughout the genome. Tumors in patients with Lynch syndrome tend to accumulate mutations in microsatellites at a much higher rate than other sequences in the genome resulting in microsatellite instability (MSI). This is due to germline mutations in mismatch repair (MMR) genes. Using small pool-polymerase chain reaction (SP-PCR), previous studies have shown that mutant alleles can be detected in microsatellites of DNA from peripheral blood lymphocytes (PBLs) of Lynch syndrome patients at frequencies that were low, but significantly higher than frequencies in PBLs of age-matched non-Lynch syndrome controls. In the present study, SP-PCR detection of frequency of mutant MSI alleles (FMMA) was performed on PBLs and saliva samples from four sets of families. Each family set consisted of a mutation carrying affected proband (initial tumor bearer), a germline mutation-carrier sibling without tumors, and an age-matched normal control, either related (for 3 family sets) without mutation carrier status or unrelated (for 1 family set) without mutation carrier status. FMMAs of saliva and PBL DNA were compared between each proband, sibling and control for each family set, and between family sets. In all five statistically significant saliva comparisons identified between germline mutation carriers (FMMA: 0.080-0.261) and normal controls (FMMA: 0.003-0.087), the measured FMMAs were always higher in the carriers (p < 0.05). A logistic regression model of the data showed a significant increase in FMMAs in saliva DNA from siblings with MMR mutation compared to the normal controls (p < 0.001). These results indicated that the increased FMMAs observed in the saliva DNA as well as PBL DNA of MMR gene mutation carriers compared to normal controls are real and repeatable. Furthermore, the logistic regression also indicated that the FMMAs seen in saliva were nearly double those seen in PBLs (p < 0.001). Saliva testing, a less-invasive procedure than PBL testing, is more sensitive and appears to be a viable alternative for identifying MSI in carriers with MMR mutations.

Authors+Show Affiliations

Molecular Genetic Technology Program, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 2, Houston, TX 77030, USA. pchu@mdanderson.orgNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

22166501

Citation

Hu, Peter, et al. "Microsatellite Instability in Saliva From Patients With Hereditary Non-polyposis Colon Cancer and Siblings Carrying Germline Mismatch Repair Gene Mutations." Annals of Clinical and Laboratory Science, vol. 41, no. 4, 2011, pp. 321-30.
Hu P, Lee CW, Xu JP, et al. Microsatellite instability in saliva from patients with hereditary non-polyposis colon cancer and siblings carrying germline mismatch repair gene mutations. Ann Clin Lab Sci. 2011;41(4):321-30.
Hu, P., Lee, C. W., Xu, J. P., Simien, C., Fan, C. L., Tam, M., Ramagli, L., Brown, B. W., Lynch, P., Frazier, M. L., Siciliano, M. J., & Coolbaugh-Murphy, M. (2011). Microsatellite instability in saliva from patients with hereditary non-polyposis colon cancer and siblings carrying germline mismatch repair gene mutations. Annals of Clinical and Laboratory Science, 41(4), 321-30.
Hu P, et al. Microsatellite Instability in Saliva From Patients With Hereditary Non-polyposis Colon Cancer and Siblings Carrying Germline Mismatch Repair Gene Mutations. Ann Clin Lab Sci. 2011;41(4):321-30. PubMed PMID: 22166501.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Microsatellite instability in saliva from patients with hereditary non-polyposis colon cancer and siblings carrying germline mismatch repair gene mutations. AU - Hu,Peter, AU - Lee,Chang Woo, AU - Xu,Jing P, AU - Simien,Crystal, AU - Fan,Chuan Li, AU - Tam,Michael, AU - Ramagli,Louis, AU - Brown,Barry W, AU - Lynch,Patrick, AU - Frazier,Marsha L, AU - Siciliano,Michael J, AU - Coolbaugh-Murphy,Mary, PY - 2011/12/15/entrez PY - 2011/12/15/pubmed PY - 2012/4/5/medline SP - 321 EP - 30 JF - Annals of clinical and laboratory science JO - Ann. Clin. Lab. Sci. VL - 41 IS - 4 N2 - Microsatellites are short tandem repeats of deoxyribonucleic acid (DNA) sequences which are distributed throughout the genome. Tumors in patients with Lynch syndrome tend to accumulate mutations in microsatellites at a much higher rate than other sequences in the genome resulting in microsatellite instability (MSI). This is due to germline mutations in mismatch repair (MMR) genes. Using small pool-polymerase chain reaction (SP-PCR), previous studies have shown that mutant alleles can be detected in microsatellites of DNA from peripheral blood lymphocytes (PBLs) of Lynch syndrome patients at frequencies that were low, but significantly higher than frequencies in PBLs of age-matched non-Lynch syndrome controls. In the present study, SP-PCR detection of frequency of mutant MSI alleles (FMMA) was performed on PBLs and saliva samples from four sets of families. Each family set consisted of a mutation carrying affected proband (initial tumor bearer), a germline mutation-carrier sibling without tumors, and an age-matched normal control, either related (for 3 family sets) without mutation carrier status or unrelated (for 1 family set) without mutation carrier status. FMMAs of saliva and PBL DNA were compared between each proband, sibling and control for each family set, and between family sets. In all five statistically significant saliva comparisons identified between germline mutation carriers (FMMA: 0.080-0.261) and normal controls (FMMA: 0.003-0.087), the measured FMMAs were always higher in the carriers (p < 0.05). A logistic regression model of the data showed a significant increase in FMMAs in saliva DNA from siblings with MMR mutation compared to the normal controls (p < 0.001). These results indicated that the increased FMMAs observed in the saliva DNA as well as PBL DNA of MMR gene mutation carriers compared to normal controls are real and repeatable. Furthermore, the logistic regression also indicated that the FMMAs seen in saliva were nearly double those seen in PBLs (p < 0.001). Saliva testing, a less-invasive procedure than PBL testing, is more sensitive and appears to be a viable alternative for identifying MSI in carriers with MMR mutations. SN - 1550-8080 UR - https://www.unboundmedicine.com/medline/citation/22166501/Microsatellite_instability_in_saliva_from_patients_with_hereditary_non_polyposis_colon_cancer_and_siblings_carrying_germline_mismatch_repair_gene_mutations_ L2 - http://www.annclinlabsci.org/cgi/pmidlookup?view=long&amp;pmid=22166501 DB - PRIME DP - Unbound Medicine ER -