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The first comprehensive genomic characterization of rectal squamous cell carcinoma
Background
Rectal cancers represent 35% of colorectal cancers; 90% are adenocarcinomas while rectal squamous cell carcinomas represents 0.3% of them. Given its rarity, little is known concerning its pathogenesis, molecular profile and therapeutic management. The current treatment trend is to treat rectal squamous cell carcinoma by analogy with anal squamous cell carcinoma with definitive chemoradiotherapy setting aside surgery in case of local recurrence.
Methods
We performed an in-depth genomic analysis (Next Generation Sequencing – 400 gene panel, Oncoscan, Human Papilloma Virus characterization) on 10 rectal squamous cell carcinoma samples and compared them in silico to those of anal squamous cell carcinoma and rectal adenocarcinoma.
Results
Rectal squamous cell carcinoma shows 100% HPV positivity. It has a similar mutational (PIK3CA, PTEN, TP53, ATM, BCL6, SOX2) and copy number variations profiles (3p deletion and 3q, 5p, 8q, 20p gain) to anal squamous cell carcinomas. PI3K/Akt/mTOR is the most commonly affected signaling pathway similarly to anal squamous cell carcinoma. In addition, common genomic alterations seen in rectal adenocarcinoma (FLT3, CDX2, GNAS BCL2, SMAD4, MALT1 mutations) were not found in these rectal squamous cases.
Conclusions
This study presents the first comprehensive genomic characterization of rectal squamous cell carcinoma. We confirm the existence of this rare histology and its molecular similarity with anal squamous cell carcinoma. This molecular proximity confirms the adequacy of therapeutic management based on histology and not localization.
Legal entity responsible for the study
The author.
Funding
Dr Astaras received a scholarship for the project entitled, "A molecular exploration of rectal squamous cell tumors to guide their management" in the context of a competition organized by the medical department of HUG (Geneva University Hospitals).
Disclosures
All authors have declared no conflicts of interest.
