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The repertoire of mutational signatures in tobacco- and non-tobacco-induced oral cancer

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Abstract

The use of tobacco products is one of the established contributors toward the development and spread of oral cancer. Additionally, recent research has indicated oral microbiome, infections with Human papilloma virus (HPV), Epstein–Barr virus (EBV), Candida as significant contributing factors to this disease along with lifestyle habits. Deregulation of cellular pathways envisaging metabolism, transcription, translation, and epigenetics caused by these risk factors either individually or in unison is manifold, resulting in the increased risk of oral cancer. Globally, this cancer continues to exist as one of the major causes of cancer-related mortalities; the numbers in the developing South Asian countries clearly indicate yearly escalation. This review encompasses the variety of genetic modifications, including adduct formation, mutation (duplication, deletion, and translocation), and epigenetic changes evident in oral squamous cell carcinoma (OSCC). In addition, it highlights the interference caused by tobacco products in Wnt signaling, PI3K/Akt/mTOR, JAK-STAT, and other important pathways. The information provided also ensures a comprehensive and critical revisit to non-tobacco-induced OSCC. Extensive literature survey and analysis has been conducted to generate the chromosome maps specifically highlighting OSCC-related mutations with the potential to act as spectacles for the early diagnosis and targeted treatment of this disease cancer.

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Abbreviations

8-OHdG:

8-Hydroxydeoxyguanosine

Akap9:

A-kinase anchoring protein 9

Akt:

Ak strain transforming

AluYb8:

Jumping gene AluYb element 8

APC:

Adenomatous polyposis coli

Arap2:

Ankyrin repeat and pH domain 2

ARID2:

AT-rich interaction domain 2

ATRX:

A-thalassemia mental retardation X-linked protein

Bcl-2:

B-cell leukemia/lymphoma 2 protein

BRAF:

Serine/threonine-protein kinase B-Raf

CASP8:

Cysteinyl aspartate protease

CD59:

Protectin

CD8 + T:

Cluster of Differentiation 8 T-cell receptor

CDH1:

E-cadherin 1

Cdh11:

Cadherin 11

CDKN2A:

Cyclin-dependent kinase inhibitor 2A

CpGIs:

CpG islands

CREBBP:

Cyclic adenosine monophosphate response element-binding protein binding protein

CSMD3:

CUB and Sushi multiple domain 3

CSp8:

Caspase 8

CTNNB1’S:

Catenin beta 1

DAPK1:

Death-associated protein kinase 1

DNA:

Deoxyribonucleic acid

DNMTs:

DNA methyltransferases

dsDNA:

Double-stranded DNA

E2F:

E2 factor

EBNA:

Epstein–Barr nuclear antigen 1

EBV:

Epstein–Barr virus

EGFR3:

Epidermal growth factor receptor 3

Ep300:

E1A-binding protein P300

ERK-MAPK:

Extracellular signal-regulated kinase

ESI:

Electrospray ionization

FANCD2:

FA complementation group D2

FAT1:

FAT atypical cadherin 1

FAT2:

FAT atypical cadherin 2

Fgf3:

Fibroblast growth factor 3

FGFR:

Fibroblast growth factor receptor

GATA4:

GATA-binding protein 4

GATS:

Global adult tobacco survey

Hjurp:

Holiday junction recognition protein

HPV:

Human papilloma virus

H-ras:

Harvey rat sarcoma virus

IARC:

International agency for research on cancer

IgA:

Immunoglobulin A

IgG:

Immunoglobulin G

IgM:

Immunoglobulin M

IL-8:

Interleukin-8

in-NETO1-1:

Neuropilin and tolloid-like 1

ISH:

In-situ hybridization

IT-MS:

Ion trap-mass spectroscopy

JAK-STAT:

Janus kinase-signal transducer and activator of transcription

JNK:

Jun N-terminal kinase

KMT2A:

Lysine methyltransferase 2A

KMT2D:

Lysine methyltransferase 2D

K-ras:

Kirsten rat sarcoma viral oncogene homolog

LINE1:

Long interspersed nuclear element 1

LMP-1:

Latent membrane protein 1

lncPSD4-1:

Long non-coding RNA PSD4-1

LRE1:

Line retro-transposable element 1

LRP1B:

LDL receptor-related protein 1B

M2BP:

Mac-2-binding protein

MDM2:

Murine double minute 2

MEF2A:

Myocyte enhancer factor 2A

MGMT:

O-6-methyl-DNA transferase

miR-181:

Micro-RNA- 181

miR-196b:

Micro-RNA 196b

miR-30a:

Micro-RNA 30a

miR-934:

Micro-RNA 934

miRNAs:

Micro-RNAs

MLH1:

MutL homolog 1

MMP9:

Matrix metalloproteinase 9

MRP14:

Migration inhibitory factor-related protein 14

mTOR:

Mammalian target of rapamycin

Muc4:

Mucin 4, Cell surface-associated

Muc6:

Mucin 6, oligomeric mucus/gel-forming

MYH1:

Myosin heavy chain

NAB:

Nitrosoanabasine

NAT:

Nitrosoanatabine

NF1:

Neurofibromatosis type 1

NF-kB:

Nuclear factor kappa B

NNAL:

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (3-pyridyl)-1- butanol

NNK:

4-Methyl nitrosamino 1,3-pyridyl butanone

NNN:

Nitrosonornicotine

NOTCH1:

Neurogenic locus notch homolog protein 1

N-ras:

Neuroblastoma RAS viral oncogene homolog

NSD1:

Nuclear receptor-binding SET domain protein 1

OSCC:

Oral squamous cell carcinoma

P14(ARF):

Tumor suppressor protein 14 alternative reading frame

P15INK4B:

Cyclin-dependent kinase 4 inhibitor B

P16:

Protein 16

P16NK4A:

P16 Cyclin-dependent kinase inhibitor 4A

P53:

Protein 53

PABPC1:

Poly (A)-binding protein cytoplasmic 1

PCR:

Polymerase chain reaction

PI3K:

Phosphatidylinositol-3-kinase

PTEN:

Phosphate and TENsin homolog deleted on chromosome 10

QqQ-MS:

Triple quadrupole-mass spectroscopy

RARB2:

Retinoic acid receptor beta 2

RASSF1/2:

Ras association domain containing protein 1

Rb:

Retinoblastoma

RB1:

Retinoblastoma 1

RNA:

Ribonucleic acid

ROS:

C-ros oncogene 1

RT-PCR:

Reverse transcriptase polymerase chain reaction

SLT:

Smokeless tobacco

SMARCA4:

Swi/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a, member 4

SOX17:

SRY-box transcription factor 17

Sp110:

Sp110 nuclear body protein

Sp140:

Sp140 nuclear body protein

STAG2:

Stromal antigen 2

TCGA:

The cancer genome atlas

TFPI2:

Tissue factor pathway inhibitor 2

TKTL1:

Transketolase-like-1

TLR9:

Toll-like receptor 9

TNF:

Tumor necrosis factor

TP53:

Tumor protein p53

TSC2:

Tuberous sclerosis complex

TSNA:

Tobacco-specific N-nitrosamination

VHL:

Von Hippel–Lindau syndrome

Wnt:

Wingless-related integration site

ZFHX3:

Zinc finger homeobox 3

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    Manish Kumar Mishra,  Shivangi, Manshi Sharma & Shelly Sehgal

  2. Department of ENT and Head and Neck Surgery, ASCOMS, Jammu, J&K, India

    Sachin Gupta

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Mishra, M.K., Gupta, S., Shivangi et al. The repertoire of mutational signatures in tobacco- and non-tobacco-induced oral cancer. Clin Transl Oncol 25, 3332–3344 (2023). https://doi.org/10.1007/s12094-023-03192-8

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