Coding and noncoding somatic mutations in candidate genes in basal cell carcinoma

• Published in: Scientific reports Vol. 10; no. 1; p. 8005
• Main Authors: Maturo, Maria Giovanna, Rachakonda, Sivaramakrishna, Heidenreich, Barbara, Pellegrini, Cristina, Srinivas, Nalini, Requena, Celia, Serra-Guillen, Carlos, Llombart, Beatriz, Sanmartin, Onofre, Guillen, Carlos, Di Nardo, Lucia, Peris, Ketty, Fargnoli, Maria Concetta, Nagore, Eduardo, Kumar, Rajiv
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 14-05-2020; Nature Publishing Group
• Subjects: 38; 45; 45/22; 45/23; 45/77; 45/90; 631/208/68/2486; 692/53/2423; Basal cell carcinoma; Biomarkers, Tumor; Carcinoma, Basal Cell - genetics; CpG islands; DNA Methylation; Epigenesis, Genetic; Etiology; Gene Expression Regulation, Neoplastic; Humanities and Social Sciences; Humans; Methylation; multidisciplinary; Mutation; Open Reading Frames; p53 Protein; Promoter Regions, Genetic; Promoters; RNA-directed DNA polymerase; Science; Science (multidisciplinary); Skin cancer; Skin Neoplasms - genetics; Statistical analysis; Tumors; Untranslated Regions
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-65057-2

Basal cell carcinoma (BCC) represents the most commonly diagnosed human cancer among persons of European ancestry with etiology mainly attributed to sun-exposure. In this study we investigated mutations in coding and flanking regions of
PTCH1
and
TP53
and noncoding alterations in the
TERT
and
DPH3
promoters in 191 BCC tumors. In addition, we measured CpG methylation within the
TERT
hypermethylated oncological region (THOR) and transcription levels of the reverse transcriptase subunit. We observed mutations in
PTCH1
in 58.6% and
TP53
in 31.4% of the tumors. Noncoding mutations in
TERT
and
DPH3
promoters were detected in 59.2% and 38.2% of the tumors, respectively. We observed a statistically significant co-occurrence of mutations at the four investigated loci. While
PTCH1
mutations tended to associate with decreased patient age at diagnosis;
TP53
mutations were associated with light skin color and increased number of nevi;
TERT
and
DPH3
promoter with history of cutaneous neoplasms in BCC patients. Increased reverse transcriptase subunit expression was observed in tumors with
TERT
promoter mutations and not with THOR methylation. Our study signifies, in addition to the protein altering mutations in the
PTCH1
and
TP53
genes, the importance of noncoding mutations in BCC, particularly functional alterations in the
TERT
promoter.