View the MathML source: Colorectal tumors manifesting high-frequency microsatellite instability (MSI-H) develop genetically as a consequence of mutations in genes harboring repetitive DNA sequences. The activin type 2 receptor (ACVR2), possessing 2 polyadenine coding sequences, was identified as a mutational target, but it is not clear if expression is abrogated. Here, we analyzed MSI-H colorectal cancers for ACVR2 mutation and expression to assess if biallelic inactivation occurs. View the MathML source: All 54 MSI-H colon cancers and 20 random microsatellite stable (MSS) tumors from a population-based cohort of 503 patients were analyzed for mutations in 2 A8 tracts (exon 3 and 10) of ACVR2 and the A10 tract of transforming growth factor β receptor 2 (TGFBR2). Additionally, we sequenced exon 10 of ACVR2 in select cancers. ACVR2 expression was determined by immunohistochemistry using an antibody targeting an epitope beyond the predicted truncated protein. View the MathML source: Forty-five of 54 MSI-H cancers (83%) showed mutation (A8 to A7) in the polyadenine tract of exon 10 compared with no MSS tumors. Of tumors with mutant ACVR2, 62% lacked protein expression but all MSS and MSI-H tumors with wild-type ACVR2 expressed protein. We found no evidence of loss of heterozygosity at the ACVR2 locus in MSS tumors. Comparatively, 69% of MSI-H cancers had frameshift mutation in TGFBR2. View the MathML source:ACVR2 mutations are highly frequent in MSI-H colon cancers and in most cases cause loss of ACVR2 expression, indicating biallelic inactivation of the gene. Loss of activin signaling through mutation of ACVR2, similar to observations with TGFBR2, may be important in the genesis of MSI-H colorectal cancer.
|Data di pubblicazione:||2012|
|Titolo:||MSH3 protein expression and nodal status in MLH1-deficient colorectal cancers.|
|Autore/i:||Laghi L; Bianchi P; Delconte G; Celesti G; Di Caro G; Pedroni M; Chiaravalli AM; Jung B; Capella C; de Leon MP; Malesci A.|
|Codice identificativo ISI:||WOS:000305900600017|
|Codice identificativo Scopus:||2-s2.0-84861783490|
|Citazione:||MSH3 protein expression and nodal status in MLH1-deficient colorectal cancers. / Laghi L; Bianchi P; Delconte G; Celesti G; Di Caro G; Pedroni M; Chiaravalli AM; Jung B; Capella C; de Leon MP; Malesci A.. - In: CLINICAL CANCER RESEARCH. - ISSN 1078-0432. - ELETTRONICO. - 18(2012), pp. 3142-3153.|
|Tipologia||Articolo su rivista|
I documenti presenti in Iris Unimore sono rilasciati con licenza Creative Commons Attribuzione - Non commerciale - Non opere derivate 3.0 Italia, salvo diversa indicazione.
In caso di violazione di copyright, contattare Supporto Iris