en en en id ca en en en en en en en en en en en en en en en en en en en en en fr en de en en en en en en en en en en en en en en ceb en en en en en en en en en en en en en en en en en en en en en en hbs_lat en en en en en en en en en en en en en en en en en en en en en en jbo en en en en en en en en en en en en en en en en en en en en en en en en en en en en en en en en en en en en en en en en fa en en en en en en en en en en en en en en en en en en en en en en en en
Molecular characterization of squamous cell carcinoma of the anal canal (SCCA) | Caris Life Sciences
B.A. Weinberg, H.J. Lenz, D. Arguello, W.S. El-Deiry, J. Xiu, Z. Gatalica, Z. Liu, S. Cheng, J.J. Hwang, P.A. Philip, A.F. Shields, J. Marshall, M.E. Salem
Nivolumab has shown promising results in SCCA patients. The majority of SCCA cases have been linked to prior human papillomavirus (HPV) infection. However, HPV negative tumors are frequently TP53 mutated and often resistant to therapy. Molecular characteristics of SCCA are largely undefined. Here we explored the underlying biology of SCCA and the differences between TP53-wild type (TP53-WT) and TP53-mutated (TP53-MT) tumors.
SCCA specimens underwent multiplatform testing with protein expression (IHC), gene amplification (ISH), and sequencing (NGS). Tumor mutational burden (TMB) was calculated using only somatic nonsynonymous missense mutations. Chi-square tests were used for comparative analyses.
In total, 253 tumors were studied. The most frequently mutated genes included PIK3CA (24%), BRCA2 (14%), FBXW7 (12.4%), TP53 (9.7%), and PTEN (8.9%). In a subset of 23 tumors subjected to Illumina NextSeq (592 gene) testing, the most common mutations were NOTCH2 (30%), NOTCH1 (27.3%), POLE (21.7%), TSC2 (17.4%), PTEN (14.3%), BRAF (13.6%), BRCA2 (13.0%), PIK3CA (13.0%), and FBXW7 (9.5%). Tumors frequently expressed MRP1 (97.6%), EGFR (92.7%), TOP2A (88.5%), TOPO1 (69.5%), MGMT (67.8%), and RRM1 (59.9%). Expression of PD-1 was seen in 55.8% (24/43) of tumors, and PD-L1 in 15.4% (9/34). HER2 was amplified in 2% (3/147) of samples, which has not been previously described in SCCA. When compared with TP53-WT (n = 93) tumors, TP53-MT (n = 10) had higher rates of BRAF (22% vs. 1%, p   17 mutations/megabase to define high vs. low TMB, 6.7% of tumors were TMB-High. High TMB did not correlate with PD-1 (p = 0.50) or PD-L1 status (p = 0.52).
Molecular profiling differences between TP53-MT and TP53- WT SCCA indicate different carcinogenic pathways and biology, which may influence response to therapy. Low frequency mutations in several druggable genes may provide therapeutic opportunities for patients with SCCA.
Caris Molecular Tumor Board
Laboratory Accreditations & Licenses
Privacy & Website Policies
Annual Notice to Physicians
© 2022 Caris Life Sciences. All rights reserved.
We use cookies on our website to give you the most relevant experience by remembering your preferences and repeat visits. By clicking “Accept,” you consent to the use of all cookies.
Do not sell my personal information.
This website uses cookies to improve your experience while you navigate through the website. Out of these, the cookies that are categorized as necessary are stored on your browser as they are essential for the working of basic functionalities of the website. We also use third-party cookies that help us analyze and understand how you use this website. These cookies will be stored in your browser only with your consent. You also have the option to opt-out of these cookies. But opting out of some of these cookies may affect your browsing experience.
Necessary cookies are absolutely essential for the website to function properly. These cookies ensure basic functionalities and security features of the website, anonymously.
This cookie is set by GDPR Cookie Consent plugin. The cookie is used to store the user consent for the cookies in the category "Analytics".
The cookie is set by GDPR cookie consent to record the user consent for the cookies in the category "Functional".
This cookie is set by GDPR Cookie Consent plugin. The cookies is used to store the user consent for the cookies in the category "Necessary".
This cookie is set by GDPR Cookie Consent plugin. The cookie is used to store the user consent for the cookies in the category "Other.
This cookie is set by GDPR Cookie Consent plugin. The cookie is used to store the user consent for the cookies in the category "Performance".
The cookie is set by the GDPR Cookie Consent plugin and is used to store whether or not user has consented to the use of cookies. It does not store any personal data.
Functional cookies help to perform certain functionalities like sharing the content of the website on social media platforms, collect feedbacks, and other third-party features.
Performance cookies are used to understand and analyze the key performance indexes of the website which helps in delivering a better user experience for the visitors.
Analytical cookies are used to understand how visitors interact with the website. These cookies help provide information on metrics the number of visitors, bounce rate, traffic source, etc.
Advertisement cookies are used to provide visitors with relevant ads and marketing campaigns. These cookies track visitors across websites and collect information to provide customized ads.
Other uncategorized cookies are those that are being analyzed and have not been classified into a category as yet.