Identifying and classifying gene mutations are critical in better understanding, and with research, eventually treating or preventing, the diseases with which they are linked.<\/p>\n
A Johns Hopkins Medicine-led research team has identified a recurrent frameshift mutation, called F722fs, in the MMS22L gene on human chromosome 6 (see graphic for the mutation\u2019s location on the chromosome), that indicates a higher risk of Ashkenazi Jewish men developing prostate cancer.<\/p>\n
Identifying and classifying gene mutations \u2014 which are the permanent changes in a person\u2019s DNA genetic code \u2014 are critical in better understanding, and with research, eventually treating or preventing, the diseases with which they are linked.<\/p>\n
A frameshift mutation occurs when one or more components (known as base pairs) of a DNA sequence are either inserted or deleted, causing the reading of the code to be shifted from normal.<\/p>\n
\u201cThis is analogous to letters being added or deleted from words in a sentence, so that the reading order is skewed and the meaning is corrupted,\u201d says study lead author William Isaacs Ph.D., the William Thomas Gerrard, Mario Anthony Duhon, and Jennifer and John Chalsty Professor of Urology (retired) at the Brady Urological Institute of the Johns Hopkins University School of Medicine.<\/p>\n
In their most recent study, Isaacs and his colleagues looked at 65 germline loss-of-function (LoF) variants \u2014 mutations in a reproductive cell (egg or sperm) that cause some genes to lose their normal functions, are passed from parent to child, and may increase the risk of certain cancers \u2014 in 3,716 Ashkenazi Jewish men who had their prostate gland removed at Johns Hopkins Medicine since 1987 to treat prostate cancer.<\/p>\n
The researchers were looking to see which of those genes \u2014 and in turn, which of their LoF mutations \u2014 were associated with a higher risk of developing prostate cancer when compared with 103,221 Ashkenazi Jewish men in a control population derived from data from around the world collected for the Genome Aggregation Database.<\/p>\n
\u201cWe found three genes with LoF mutations in the case group where the man had significantly higher rates of prostate cancer than in the control group,\u201d says Isaacs. \u201cTo validate our finding, we looked at the three genes in two groups of Ashkenazi Jewish men from a United Kingdom database \u2014 107 who had been treated for prostate cancer and some 1,200 as a control population \u2014 and found that one of the three genes, MMS22L, continued to be linked to higher rates of the disease.\u201d<\/p>\n
Further analysis by the researchers, says Isaacs, revealed that the vast majority of the men with prostate cancer from the Johns Hopkins and UK groups who carried the MMS22L gene also had the same LoF variant, a frameshift mutation known as F722fs.<\/p>\n
Looking at data from three other patient groups (University of Michigan\/Duke University, NorthShore University HealthSystem and GoPath Labs) of Ashkenazi Jewish men who had prostate cancer, the researchers again found a solid association with the F722fs mutation.<\/p>\n
Isaacs says that the positive correlation he and his colleagues found between the mutated MMS22L gene and prostate cancer risk in Ashkenazi Jewish men is comparable to other known DNA repair gene mutations linked to increased prostate cancer risk for that population, such as the well-known BRCA2.<\/p>\n
Additionally, the researchers found their data indicates that Ashkenazi Jewish men with the F722fs mutation also may be linked to two other characteristics of note, one negative and the other positive.<\/p>\n
\u201cWe learned that those with the F722fs mutation who developed prostate cancer were likely to have more aggressive forms of the disease,\u201d says Isaacs. \u201cOn the other hand, we know that the MMS22L gene makes a person more responsive to a prostate cancer treatment known as PARP inhibition, so perhaps the F722fs mutation may play a role in that sensitivity \u2014 a role that we might be able to leverage for improving the therapy. However, we did not look at that in this latest study.\u201d<\/p>\n
In future research, Isaacs says he and his colleagues hope to learn more about the F722fs LoF mutation, especially how it might be used as a tool for both screening an Ashkenazi Jewish man\u2019s risk of developing prostate cancer and predicting which of those men will benefit most from a PARP inhibitor as part of their treatment should they get the disease.<\/p>\n","protected":false},"excerpt":{"rendered":"Identifying and classifying gene mutations are critical in better understanding, and with research, eventually treating or preventing, the…\n","protected":false},"author":2,"featured_media":399360,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[3846],"tags":[267,105,12,70,16,15],"class_list":{"0":"post-399359","1":"post","2":"type-post","3":"status-publish","4":"format-standard","5":"has-post-thumbnail","7":"category-genetics","8":"tag-genetics","9":"tag-health","10":"tag-news","11":"tag-science","12":"tag-uk","13":"tag-united-kingdom"},"share_on_mastodon":{"url":"https:\/\/pubeurope.com\/@uk\/115150451105176141","error":""},"_links":{"self":[{"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/posts\/399359","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/comments?post=399359"}],"version-history":[{"count":0,"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/posts\/399359\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/media\/399360"}],"wp:attachment":[{"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/media?parent=399359"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/categories?post=399359"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/tags?post=399359"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}