Epigenetic silencing of lncRNA MORT in 16 TCGA cancer types

Our plain-English summary of Epigenetic silencing of lncRNA MORT in 16 TCGA cancer types, by L. Vrba, B.W. Futscher (F1000Research, 2018).

The study

• Authors: L. Vrba, B.W. Futscher
• Journal: F1000Research
• Published: 2018;7:211
• Cited by: 31 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

We have previously described a hominid-specific long non-coding RNA, MORT (also known as ZNF667-AS1, Gene ID: 100128252), which is expressed in all normal cell types, but epigenetically silenced during cancer-associated immortalization of human mammary epithelial cells. Initial analysis of The Cancer Genome Atlas (TCGA) showed that 15 of 17 cancer types, which represent the 10 most common cancers in women and men, display DNA methylation associated MORT silencing in a large fraction of their tumors. In this study we analyzed MORT expression and DNA methylation state in the remaining 16 TCGA cancer types not previously reported. Seven of the 16 cancer types showed DNA methylation linked MORT silencing in a large fraction of their tumors. These are carcinomas (cervical cancer, and cancers of esophagus, stomach, and bile duct), and the non-epithelial tumors mesothelioma, sarcoma, and uterine carcinosarcoma. Together with the findings from our previous report, MORT expression is silenced by aberrant DNA methylation in 22 of 33 of TCGA cancer types. These 22 cancers include most carcinoma types, blood derived cancers and sarcomas. In conclusion, results suggest that the MORT gene is one of the most common epigenetic aberrations seen in human cancer. Coupled with the timing of MORT gene silencing during in vitro epithelial cell immortalization and its occurrence early in the temporal arc of human carcinogenesis, this provides strong circumstantial evidence for a tumor suppressor role for MORT.

In plain English

This research note used public data from The Cancer Genome Atlas (TCGA) to ask whether a gene called MORT is switched off by DNA methylation (a chemical marking of DNA) in 16 cancer types the authors had not examined before. They compared MORT RNA levels with methylation of the gene's promoter region in each tumor sample. Seven types showed what the authors called strong methylation-linked MORT silencing: cervical, bile duct, esophageal and stomach cancers, mesothelioma, sarcoma and uterine carcinosarcoma. The mesothelioma data came from 87 tumor samples and no normal tissue samples. The article does not say where in the body these mesotheliomas arose. More than 75% of 304 cervical tumor samples had MORT methylated and silenced. Adding their earlier work, the authors counted 22 of 33 TCGA cancer types with this silencing. They noted that most of the 16 types lacked normal tissue samples for comparison. The authors concluded that MORT silencing is one of the most common epigenetic changes in human cancer, and that this strongly supports a tumor-suppressing role for MORT.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Research note: analysis of publicly available tumor genomic data (TCGA RNA-seq and DNA methylation microarray data), extending the authors' earlier analysis
• Who was studied: Primary tumor samples, and where available normal samples, from 16 TCGA cancer types. Mesothelioma (MESO) contributed 87 tumor samples and 0 normal samples. Cervical cancer (CESC) contributed 304 tumor samples and 3 normal samples.
• Exposure: No asbestos or other environmental exposure was studied. The factor examined was DNA methylation of 7 CpG sites in the MORT gene promoter, compared with MORT RNA expression.
• Main results:
  • Seven of the 16 cancer types showed strong MORT silencing by DNA methylation: CESC (cervical), CHOL (bile duct), ESCA (esophageal), MESO (mesothelioma), SARC (sarcoma), STAD (stomach) and UCS (uterine carcinosarcoma).
  • In these seven types, the correlation (rho) between MORT expression and methylation was below -0.5. Some tumor samples exceeded 0.5 beta (more than 50% methylation), and a large fraction of tumor samples had very low to no MORT expression.
  • In the remaining nine types the correlation was also negative, but with little or no silencing. Promoter methylation was very low in UVM. Very few tumors had MORT silenced in ACC, KICH, OV and THYM. GBM, LGG, PCPG and TGCT did not appear to show MORT silencing.
  • In cervical tumors, more than 75% of 304 samples had a hypermethylated MORT promoter and MORT silenced.
  • Combined with the authors' previous report, MORT was silenced by DNA methylation in 22 of 33 TCGA cancer types.
• The authors' conclusion: The authors concluded that the MORT gene is one of the most common epigenetic aberrations seen in human cancer. Together with MORT silencing occurring early in carcinogenesis, they wrote that this strongly supports a tumor suppressive role for MORT.
• Limitations the authors state:
  • Most of the 16 cancer types lacked normal tissue samples, and some had fewer tumor samples than the cancer types in the authors' original study.
  • For ovarian cancer (OV), few samples had the main methylation platform data. Data from an older platform covering only 2 of the 7 CpG sites were used instead.

Topics

Medical terms in this study, explained in our Lexicon: Carcinoma, Mesothelioma, Sarcoma, Carcinogenesis.

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