Abstract
Purpose: Microsatellite instability (MSI) testing of colorectal cancer tumors is used as a screening tool to identify patients most likely to be mismatch repair (MMR) gene mutation carriers. We wanted to examine which microsatellite markers currently used to detect MSI best predict early-onset colorectal cancer caused by germ-line mutations in MMR genes.
Experimental Design: Invasive primary tumors from a population-based sample of 107 cases of colorectal cancer diagnosed before age 45 years and tested for germ-line mutations in MLHI, MSH2, MSH6, and PMS2 and MMR protein expression were screened for MSI using the National Cancer Institute panel and an expanded 10-microsatellite marker panel.
Results: The National Cancer Institute five-marker panel system scored 31 (29%) as NCIMSI-High, 13 (12%) as NCIMSI-Low, and 63 (59%) as NCIMS-Stable. The 10-marker panel classified 18 (17%) as 10MSI-High, 17 (16%) as 10MSI-Low, and 72 (67%) as 10MS-Stable. Of the 26 cancers that lacked the expression of at least one MMR gene, 24 (92%) were positive for some level of MSI (using either microsatellite panel). The mononucleotide repeats Bat26, Bat40, and Myb were unstable in all 10MSI-High cancers and all MLHI and MSH2 mutation carriers (100% sensitive). Bat40 and Bat25 were unstable in all tumors of MSH6 mutation carriers (100% sensitive). Bat40 was unstable in all MMR gene mutation carriers (100% sensitive). By incorporating seven mononucleotide repeats markers into the 10-marker panel, we were able to distinguish the carriers of MSH6 mutations (all scored 10MSI-Low) from the MLHI and MSH2 mutation carriers (all scored 10MSI-High).
Conclusions: In early-onset colorectal cancer, a microsatellite panel containing a high proportion of mononuclear repeats can distinguish between tumors caused by MLH1 and MSH2 mutations from those caused by MSH6 mutations.
| Original language | English |
|---|---|
| Pages (from-to) | 2865-2869 |
| Number of pages | 5 |
| Journal | Clinical Cancer Research |
| Volume | 13 |
| Issue number | 10 |
| DOIs | |
| Publication status | Published - 15 May 2007 |
| Externally published | Yes |
Cite this
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Microsatellite instability markers for identifying early-onset colorectal cancers caused by germ-line mutations in DNA mismatch repair genes. / Mead, Leeanne J.; Jenkins, Mark A.; Young, Joanne; Royce, Simon G.; Smith, Letitia; St. John, D. James B; Macrae, Finlay; Giles, Graham G.; Hopper, John L.; Southey, Melissa C.
In: Clinical Cancer Research, Vol. 13, No. 10, 15.05.2007, p. 2865-2869.Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - Microsatellite instability markers for identifying early-onset colorectal cancers caused by germ-line mutations in DNA mismatch repair genes
AU - Mead, Leeanne J.
AU - Jenkins, Mark A.
AU - Young, Joanne
AU - Royce, Simon G.
AU - Smith, Letitia
AU - St. John, D. James B
AU - Macrae, Finlay
AU - Giles, Graham G.
AU - Hopper, John L.
AU - Southey, Melissa C.
PY - 2007/5/15
Y1 - 2007/5/15
N2 - Purpose: Microsatellite instability (MSI) testing of colorectal cancer tumors is used as a screening tool to identify patients most likely to be mismatch repair (MMR) gene mutation carriers. We wanted to examine which microsatellite markers currently used to detect MSI best predict early-onset colorectal cancer caused by germ-line mutations in MMR genes. Experimental Design: Invasive primary tumors from a population-based sample of 107 cases of colorectal cancer diagnosed before age 45 years and tested for germ-line mutations in MLHI, MSH2, MSH6, and PMS2 and MMR protein expression were screened for MSI using the National Cancer Institute panel and an expanded 10-microsatellite marker panel. Results: The National Cancer Institute five-marker panel system scored 31 (29%) as NCIMSI-High, 13 (12%) as NCIMSI-Low, and 63 (59%) as NCIMS-Stable. The 10-marker panel classified 18 (17%) as 10MSI-High, 17 (16%) as 10MSI-Low, and 72 (67%) as 10MS-Stable. Of the 26 cancers that lacked the expression of at least one MMR gene, 24 (92%) were positive for some level of MSI (using either microsatellite panel). The mononucleotide repeats Bat26, Bat40, and Myb were unstable in all 10MSI-High cancers and all MLHI and MSH2 mutation carriers (100% sensitive). Bat40 and Bat25 were unstable in all tumors of MSH6 mutation carriers (100% sensitive). Bat40 was unstable in all MMR gene mutation carriers (100% sensitive). By incorporating seven mononucleotide repeats markers into the 10-marker panel, we were able to distinguish the carriers of MSH6 mutations (all scored 10MSI-Low) from the MLHI and MSH2 mutation carriers (all scored 10MSI-High). Conclusions: In early-onset colorectal cancer, a microsatellite panel containing a high proportion of mononuclear repeats can distinguish between tumors caused by MLH1 and MSH2 mutations from those caused by MSH6 mutations.
AB - Purpose: Microsatellite instability (MSI) testing of colorectal cancer tumors is used as a screening tool to identify patients most likely to be mismatch repair (MMR) gene mutation carriers. We wanted to examine which microsatellite markers currently used to detect MSI best predict early-onset colorectal cancer caused by germ-line mutations in MMR genes. Experimental Design: Invasive primary tumors from a population-based sample of 107 cases of colorectal cancer diagnosed before age 45 years and tested for germ-line mutations in MLHI, MSH2, MSH6, and PMS2 and MMR protein expression were screened for MSI using the National Cancer Institute panel and an expanded 10-microsatellite marker panel. Results: The National Cancer Institute five-marker panel system scored 31 (29%) as NCIMSI-High, 13 (12%) as NCIMSI-Low, and 63 (59%) as NCIMS-Stable. The 10-marker panel classified 18 (17%) as 10MSI-High, 17 (16%) as 10MSI-Low, and 72 (67%) as 10MS-Stable. Of the 26 cancers that lacked the expression of at least one MMR gene, 24 (92%) were positive for some level of MSI (using either microsatellite panel). The mononucleotide repeats Bat26, Bat40, and Myb were unstable in all 10MSI-High cancers and all MLHI and MSH2 mutation carriers (100% sensitive). Bat40 and Bat25 were unstable in all tumors of MSH6 mutation carriers (100% sensitive). Bat40 was unstable in all MMR gene mutation carriers (100% sensitive). By incorporating seven mononucleotide repeats markers into the 10-marker panel, we were able to distinguish the carriers of MSH6 mutations (all scored 10MSI-Low) from the MLHI and MSH2 mutation carriers (all scored 10MSI-High). Conclusions: In early-onset colorectal cancer, a microsatellite panel containing a high proportion of mononuclear repeats can distinguish between tumors caused by MLH1 and MSH2 mutations from those caused by MSH6 mutations.
UR - http://www.scopus.com/inward/record.url?scp=34249792086&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-06-2174
DO - 10.1158/1078-0432.CCR-06-2174
M3 - Article
VL - 13
SP - 2865
EP - 2869
JO - Clinical Cancer Research
JF - Clinical Cancer Research
SN - 1078-0432
IS - 10
ER -