Frequent concomitant inactivation of miR-34a and miR-34b/c by CpG methylation in colorectal, pancreatic, mammary, ovarian, urothelial, and renal cell carcinomas and soft tissue sarcomas
The microRNA encoding genes miR-34a and miR-34b/c represent direct p53 target genes and possess tumor suppressive properties as they mediate apoptosis, cell cycle arrest, and senescence. We previously reported that the miR-34a gene is subject to epigenetic inactivation by CpG methylation of its prom...
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| Vydáno v: | Virchows Archiv : an international journal of pathology Ročník 458; číslo 3; s. 313 - 322 |
|---|---|
| Hlavní autoři: | , , , , , , , , |
| Médium: | Journal Article |
| Jazyk: | angličtina |
| Vydáno: |
Berlin/Heidelberg
Springer-Verlag
01.03.2011
Springer Springer Nature B.V |
| Témata: | |
| ISSN: | 0945-6317, 1432-2307, 1432-2307 |
| On-line přístup: | Získat plný text |
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| Shrnutí: | The microRNA encoding genes
miR-34a
and
miR-34b/c
represent direct p53 target genes and possess tumor suppressive properties as they mediate apoptosis, cell cycle arrest, and senescence. We previously reported that the
miR-34a
gene is subject to epigenetic inactivation by CpG methylation of its promoter region in primary prostate cancer and melanomas, and in 110 different cancer cell lines of diverse origin. Here we analyzed the methylation status of
miR-34a
and
miR-34b/c
in additional primary tumors of divergent sites. We found methylation of
miR-34a
or
miR-34b/c
in formalin-fixed, paraffin-embedded (FFPE) tumor samples from 178 patients with the following frequencies: colorectal cancer (74%
miR-34a
, 99%
miR-34b/c
;
n
= 114), pancreatic cancer (64%, 100%;
n
= 11), mammary cancer (60%, 90%;
n
= 10), ovarian cancer (62%, 69%;
n
= 13), urothelial cancer (71%, 57%;
n
= 7), and renal cell cancer (58%, 100%;
n
= 12). Furthermore, soft tissue sarcomas showed methylation of
miR-34
gene promoters in FFPE samples (64%, 45%;
n
= 11), in explanted, cultured cells (53%, 40%;
n
= 40), and in frozen tissue samples (75%, 75%,
n
= 8). In the colorectal cancer samples a statistically significant correlation of
miR-34a
methylation and the absence of p53 mutation was detected. With the exception of sarcoma cell lines, the inactivation of
miR-34a
and
miR-34b/c
was concomitant in most cases. These results show that
miR-34
inactivation is a common event in tumor formation, and suggest that CpG methylation of
miR-34a
and
miR-34-b/c
may have diagnostic value. The mutual exclusiveness of
miR-34a
methylation and p53 mutation indicates that
miR-34a
inactivation may substitute for loss of p53 function in cancer. |
|---|---|
| Bibliografie: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 14 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 |
| ISSN: | 0945-6317 1432-2307 1432-2307 |
| DOI: | 10.1007/s00428-010-1030-5 |