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We attempted to explore a novel auxiliary method for differential diagnosis between ACC with benign adrenocortical adenoma (ACA), based on mutations of target genes in tissues. Nine genes were chosen as target genes, including\n                    <jats:italic>TP53, CTNNB1, ARMC5, PRKAR1A, ZNRF3, RB1, APC, MEN1,<\/jats:italic>\n                    and\n                    <jats:italic>RPL22<\/jats:italic>\n                    . Exons sequencing of target genes were performed in 98 cases of tissue samples by FastTarget technology, including 41 ACC tissues, 32 ACA tissues, and 25 normal adrenal gland tissues. Significant mutations were detected and identified, and the clinical information was collected, for further comparative analysis and application to assist differential diagnosis of ACC. We identified 132 significant gene mutations and 227 significant mutation sites in 37 ACC tissues, much more than ACA and normal adrenal gland tissues. Mutation rates of 6 genes in ACC tissues were obviously higher than ACA tissues, including\n                    <jats:italic>ZNRF3, ARMC5, TP53, APC, RB1,<\/jats:italic>\n                    and\n                    <jats:italic>PRKAR1A<\/jats:italic>\n                    , regarded as high-risk genes. The sum of mutated high-risk genes detected in each sample was denominated sum of high-risk gene mutation (SHGM), and the rates of SHGM\u2009&gt;\u20090 and SHGM\u2009&gt;\u20091 in ACC tissues were 73.0% and 62.2%, respectively, both obviously higher than those in ACA tissues, with significant statistic differences. Especially for 8 cases of ACC with diameter\u2009&lt;\u20095\u00a0cm, SHGM\u2009&gt;\u20090 and SHGM\u2009&gt;\u20091 were found in 6 samples (75%) and 4 samples (50%), respectively. However, no relevance was found between SHGM and clinical characteristics of ACC. We identified 6 high-risk genes in ACC tissues, with significantly higher mutation rates than ACA or normal adrenal gland tissues. The sum of mutated high-risk genes detected in ACC tissues was denominated SHGM, which was potential to assist the differential diagnosis of ACC with ACA, especially for the small-size ACC.\n                  <\/jats:p>","DOI":"10.1007\/s10528-021-10039-w","type":"journal-article","created":{"date-parts":[[2021,2,10]],"date-time":"2021-02-10T00:11:08Z","timestamp":1612915868000},"page":"902-918","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Sum of High-Risk Gene Mutation (SHGM): A Novel Attempt to Assist Differential Diagnosis for Adrenocortical Carcinoma with Benign Adenoma, Based on Detection of Mutations of Nine Target Genes"],"prefix":"10.1007","volume":"59","author":[{"given":"Guo-Yang","family":"Zheng","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xue-Bin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7676-0255","authenticated-orcid":false,"given":"Han-Zhong","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu-Shi","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jian-Hua","family":"Deng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xing-Cheng","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,2,9]]},"reference":[{"issue":"2","key":"10039_CR1","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1677\/joe.0.1650223","volume":"165","author":"J Arola","year":"2000","unstructured":"Arola J, Liu J, Heikkil\u00e4 P et al (2000) Expression of inhibin alpha in adrenocortical tumours reflects the hormonal status of the neoplasm. 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This study had been approved by the PUMCH Institutional Review Board, and the approval was papery report. We could send the electronic scanning report to the editors or reviewers if it is needed.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical Approval"}},{"value":"Informed consent was obtained from all individual participants included in this study.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to Participate"}},{"value":"All patients involved in this study have signed to approve the publication of their medical information.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for Publication"}}]}}