{"id":5261,"date":"2018-09-12T16:00:00","date_gmt":"2018-09-12T16:00:00","guid":{"rendered":"https:\/\/www.cancer.gov\/news-events\/cancer-currents-blog\/2018\/appendix-cancer-genetic-distinct"},"modified":"2024-11-03T15:17:33","modified_gmt":"2024-11-03T15:17:33","slug":"appendix-cancers-are-genetically-distinct-from-other-gastrointestinal-cancers-study-shows","status":"publish","type":"post","link":"https:\/\/ogkologos.com\/en\/appendix-cancers-are-genetically-distinct-from-other-gastrointestinal-cancers-study-shows\/","title":{"rendered":"Appendix Cancers Are Genetically Distinct from Other Gastrointestinal Cancers, Study Shows"},"content":{"rendered":"

September 12, 2018, by NCI Staff<\/p>\n

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The appendix is located at the end of the large intestine.<\/p>\n

Credit: National Cancer Institute<\/p>\n<\/div>\n<\/figcaption><\/figure>\n

The largest-ever study of DNA changes in cancer of the appendix<\/a> shows that this rare cancer is distinct from colorectal cancer and other cancers of the gastrointestinal (GI) system<\/a>. Moreover, the study authors reported that specific genetic mutations<\/a> found in the tumors may help predict whether they are likely to be aggressive.\u00a0<\/p>\n

When cancer of the appendix cannot be removed completely with surgery, the standard treatment is to give patients the same chemotherapy regimens used to treat colorectal cancer.<\/p>\n

But recent studies analyzing the molecular characteristics of appendiceal cancers have suggested that approaching them as if they are the same as other GI cancers may be a mistake. The new study confirms that appendix cancer is \u201cvery different from colon cancer,\u201d said John Paul Shen, M.D., one of the leaders of the study and a postdoctoral fellow at the University of California, San Diego (UCSD).<\/p>\n

\u201cIt stands to reason,\u201d Dr. Shen continued, \u201cthat we should develop treatments specifically for appendix cancer, rather than give these patients chemotherapy that was tested on colon cancer patients.\u201d<\/p>\n

The study was published online on August 8 in JCO Precision Oncology<\/em>.<\/p>\n

One Tumor Is Not Like the Other<\/h2>\n

The new study analyzed the DNA sequences of more than 300 cancer-associated genes in appendix tumor tissue from 703 patients using a test developed by the company Foundation Medicine. Last November, the Food and Drug Administration approved the Foundation Medicine gene panel as one of the first comprehensive genome-profiling tests for tumors. \u00a0<\/p>\n

The frequency of mutations in important cancer genes clearly differed in the appendiceal cancers compared with colorectal and pancreatic cancers analyzed in earlier studies, Dr. Shen and his colleagues reported. For example, the TP53<\/em> and APC<\/em> genes were far less likely to be mutated in appendiceal cancers than in colorectal cancer.<\/p>\n

Mutation frequencies also differed among appendiceal cancer subtypes (as defined by their appearance, or histopathology<\/a>)<\/span>. For example, mutations in the KRAS<\/em> gene were common in adenocarcinomas<\/a>, which begin in the lining of the appendix, but were much less frequent in a subtype known as goblet cell carcinoids.<\/p>\n

Mutation Profiles Associated with Prognosis<\/h2>\n

One of the most striking findings was the difference in prognosis for patients whose tumors had mutations in the GNAS<\/em> gene compared with patients whose tumors had mutations in the TP53<\/em> gene.<\/p>\n

In a group\u00a0of 76 patients who were treated at UCSD, those with GNAS<\/em> mutations had a life expectancy of 10 years after diagnosis, whereas patients with TP53<\/em> mutations had a life expectancy of 3 years. Patients whose tumors had neither mutation had a life expectancy of 6 years.<\/p>\n

In addition, GNAS<\/em> mutations were almost never found in tumors that grow and spread quickly (high-grade<\/a> tumors). The authors noted that this finding suggests that low-grade<\/a> tumors with GNAS<\/em> mutations don\u2019t develop into high-grade tumors. By contrast, TP53<\/em> mutations were associated with poorer outcomes regardless of tumor grade.<\/p>\n

Dr. Shen said he doesn\u2019t expect this data to change clinical practice yet, but added, \u201cGiven that so much of the time as an oncologist you have so little data to guide you, especially for a rare tumor, I think any data is helpful.\u201d<\/p>\n

Carmen Allegra, M.D., head of GI Cancer Therapeutics in NCI\u2019s Cancer Therapy Evaluation Program<\/a>, commented that it is \u201cof great value to have this sort of information\u201d for a cancer that is relatively rare and not well understood. This kind of work can drive more research and the search for \u201cspecific and better\u201d treatments, Dr. Allegra said.<\/p>\n

To develop more effective treatments for appendiceal cancer, Dr. Shen suggested that researchers may need to begin classifying these cancers by molecular type, rather than considering all appendix tumors as a single cancer type or a type of colorectal cancer.<\/p>\n

The addition of molecular typing may also serve as way to simplify tumor classification, Dr. Shen said. A 2017 study showed that pathologists give conflicting classifications for appendix cancer tumors<\/a> nearly 30% of the time.<\/p>\n

Anirban Maitra, M.B.B.S., a professor of pathology specializing in pancreatic cancer at The University of Texas MD Anderson Cancer Center, agreed that \u201cit is absolutely critical that a tumor is, first and foremost, correctly classified.\u201d He added that while \u201chistopathology still remains the gold standard,\u201d molecular typing is complementary and is increasingly helping provide \u201cmore refined subtyping.\u201d<\/p>\n

Ramifications and Future Directions<\/h2>\n

While the study provides evidence that analyzing fewer\u00a0than 10 genes can be very informative in classifying an appendiceal tumor, the study didn\u2019t unearth \u201cactionable mutations,\u201d or mutations in genes for which targeted drugs are already available, both Drs. Shen and Maitra pointed out.<\/p>\n

However, a small proportion of patients\u2019 tumors had an alteration known as microsatellite instability<\/a> high (MSI-H), which can cause tumors to develop many genetic mutations. Pembrolizumab (Keytruda)<\/a> has been approved by the Food and Drug Administration for the treatment of patients with MSI-H tumors, regardless of their cancer type<\/a>, and Dr. Shen suggested that this treatment option should be considered for people with appendix cancers whose tumors are MSI-H.<\/p>\n

The study raises other prospects for further investigation. For example, Dr. Shen would like to know whether surgical removal alone is enough to cure appendiceal cancers with GNAS<\/em> mutations. Dr. Shen also noted that more work is needed to address how best to treat advanced appendix cancers with TP53<\/em> mutations, which he said should be studied separately from other tumors.<\/p>\n

Researchers are beginning to develop cell line models of different appendiceal cancer subtypes based on their molecular profiles, Dr. Shen said, so they can begin testing therapies that might work best against each subtype.\u00a0<\/p>\n

Source<\/a><\/p>","protected":false},"excerpt":{"rendered":"

September 12, 2018, by NCI Staff The appendix is located at the end of the large intestine. Credit: National Cancer Institute The largest-ever study of DNA changes in cancer of the appendix shows that this rare cancer is distinct from colorectal cancer and other cancers of the gastrointestinal (GI) system. Moreover, the study authors reported […]<\/p>\n","protected":false},"author":2,"featured_media":5262,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_monsterinsights_skip_tracking":false,"footnotes":""},"categories":[5137],"tags":[],"class_list":["post-5261","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-world-news"],"_links":{"self":[{"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/posts\/5261","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/comments?post=5261"}],"version-history":[{"count":1,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/posts\/5261\/revisions"}],"predecessor-version":[{"id":42844,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/posts\/5261\/revisions\/42844"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/media\/5262"}],"wp:attachment":[{"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/media?parent=5261"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/categories?post=5261"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/tags?post=5261"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}