TY - JOUR
T1 - Comparing genomic landscapes of oral and cutaneous squamous cell carcinoma of the head and neck
T2 - quest for novel diagnostic markers
AU - Gupta, Ruta
AU - Strbenac, Dario
AU - Satgunaseelan, Laveniya
AU - Cheung, Veronica Ka Yan
AU - Narayanappa, Harini
AU - Ashford, Bruce
AU - Mitchell, Jenny
AU - Thind, Amarinder
AU - Palme, Carsten E.
AU - Ch'ng, Sydney
AU - Low, Tsu Hui (Hubert)
AU - Wykes, James
AU - Willet, Cali E.
AU - Chew, Tracy
AU - Yang, Jean
AU - Ranson, Marie
AU - Clark, Jonathan R.
PY - 2023/8
Y1 - 2023/8
N2 - Squamous cell carcinoma is the most common head and neck malignancy arising from the oral mucosa and the skin. The histologic and immunohistochemical features of oral squamous cell carcinoma (OSCC) and head and neck cutaneous squamous cell carcinoma (HNcSCC) are similar, making it difficult to identify the primary site in cases of metastases. With the advent of immunotherapy, reliable distinction of OSCC and HNcSCC at metastatic sites has important treatment and prognostic implications. Here, we investigate and compare the genomic landscape of OSCC and HNcSCC to identify diagnostically useful biomarkers. Whole-genome sequencing data from 57 OSCC and 41 HNcSCC patients were obtained for tumor and matched normal samples. Tumor mutation burden (TMB), Catalogue of Somatic Mutations in Cancer (COSMIC) mutational signatures, frequent chromosomal alterations, somatic single nucleotide, and copy number variations were analyzed. The median TMB of 3.75 in primary OSCC was significantly lower (P <.001) than that of 147.51 mutations/Mb in primary HNcSCC. The COSMIC mutation signatures were significantly different (P <.001) between OSCC and HNcSCC. OSCC showed COSMIC single-base substitution (SBS) mutation signature 1 and AID/APOBEC activity–associated signature 2 and/or 13. All except 1 HNcSCC from hair-bearing scalp showed UV damage–associated COSMIC SBS mutation signature 7. Both OSCC and HNcSCC demonstrated a predominance of tumor suppressor gene mutations, predominantly TP53. The most frequently mutated oncogenes were PIK3CA and MUC4 in OSCC and HNcSCC, respectively. The metastases of OSCC and HNcSCC demonstrated TMB and COSMIC SBS mutation signatures similar to their primary counterparts. The combination of high TMB and UV signature in a metastatic keratinizing squamous cell carcinoma suggests HNcSCC as the primary site and may also facilitate decisions regarding immunotherapy. HNcSCC and OSCC show distinct genomic profiles despite histologic and immunohistochemical similarities. Their genomic characteristics may underlie differences in behavior and guide treatment decisions in recurrent and metastatic settings.
AB - Squamous cell carcinoma is the most common head and neck malignancy arising from the oral mucosa and the skin. The histologic and immunohistochemical features of oral squamous cell carcinoma (OSCC) and head and neck cutaneous squamous cell carcinoma (HNcSCC) are similar, making it difficult to identify the primary site in cases of metastases. With the advent of immunotherapy, reliable distinction of OSCC and HNcSCC at metastatic sites has important treatment and prognostic implications. Here, we investigate and compare the genomic landscape of OSCC and HNcSCC to identify diagnostically useful biomarkers. Whole-genome sequencing data from 57 OSCC and 41 HNcSCC patients were obtained for tumor and matched normal samples. Tumor mutation burden (TMB), Catalogue of Somatic Mutations in Cancer (COSMIC) mutational signatures, frequent chromosomal alterations, somatic single nucleotide, and copy number variations were analyzed. The median TMB of 3.75 in primary OSCC was significantly lower (P <.001) than that of 147.51 mutations/Mb in primary HNcSCC. The COSMIC mutation signatures were significantly different (P <.001) between OSCC and HNcSCC. OSCC showed COSMIC single-base substitution (SBS) mutation signature 1 and AID/APOBEC activity–associated signature 2 and/or 13. All except 1 HNcSCC from hair-bearing scalp showed UV damage–associated COSMIC SBS mutation signature 7. Both OSCC and HNcSCC demonstrated a predominance of tumor suppressor gene mutations, predominantly TP53. The most frequently mutated oncogenes were PIK3CA and MUC4 in OSCC and HNcSCC, respectively. The metastases of OSCC and HNcSCC demonstrated TMB and COSMIC SBS mutation signatures similar to their primary counterparts. The combination of high TMB and UV signature in a metastatic keratinizing squamous cell carcinoma suggests HNcSCC as the primary site and may also facilitate decisions regarding immunotherapy. HNcSCC and OSCC show distinct genomic profiles despite histologic and immunohistochemical similarities. Their genomic characteristics may underlie differences in behavior and guide treatment decisions in recurrent and metastatic settings.
KW - cutaneous
KW - head and neck
KW - keratinizing squamous cell carcinoma
KW - mutation signature
KW - tumor mutation burden
KW - whole-genome sequencing
UR - http://www.scopus.com/inward/record.url?scp=85168315824&partnerID=8YFLogxK
U2 - 10.1016/j.modpat.2023.100190
DO - 10.1016/j.modpat.2023.100190
M3 - Article
C2 - 37080394
AN - SCOPUS:85168315824
SN - 0893-3952
VL - 36
SP - 1
EP - 9
JO - Modern Pathology
JF - Modern Pathology
IS - 8
M1 - 100190
ER -