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Genetic determinants in head and neck squamous cell carcinoma and their influence on global personalized medicine

View Article: PubMed Central - PubMed

ABSTRACT

While sequencing studies have provided an improved understanding of the genetic landscape of head and neck squamous cell carcinomas (HNSCC), there remains a significant lack of genetic data derived from non-Caucasian cohorts. Additionally, there is wide variation in HNSCC incidence and mortality worldwide both between and within various geographic regions. These epidemiologic differences are in part accounted for by varying exposure to environmental risk factors such as tobacco, alcohol, high risk human papilloma viruses and betel quid. However, inherent genetic factors may also play an important role in this variability. As limited sequencing data is available for many populations, the involvement of unique genetic factors in HNSCC pathogenesis from epidemiologically diverse groups is unknown. Here, we review current knowledge about the epidemiologic, environmental, and genetic variation in HNSCC cohorts globally and discuss future studies necessary to further our understanding of these differences. Long-term, a more complete understanding of the genetic drivers found in diverse HNSCC cohorts may help the development of personalized medicine protocols for patients with rare or complex genetic events.

No MeSH data available.


Related in: MedlinePlus

Global variation in frequency of PIK3CA aberration in oral cancerFrequency of PIK3CA amplification (A) and mutation (B) in oral cancer cohorts from countries worldwide. Based on data from Murugan et al. [94] and review of more recent literature, as detailed in Table S2.
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Figure 6: Global variation in frequency of PIK3CA aberration in oral cancerFrequency of PIK3CA amplification (A) and mutation (B) in oral cancer cohorts from countries worldwide. Based on data from Murugan et al. [94] and review of more recent literature, as detailed in Table S2.

Mentions: Rates of PIK3CA aberration have been assessed in various global cohorts [95–100] and are shown in Figure 6. Low frequencies of gene amplification were observed in 3/33 (9%) patients in a German HNSCC cohort as well as 3/115 (2.3%) and 6/50 (12%) individuals in two independent Japanese groups [96, 98, 101]. Alternatively, Redon et al. noted 6/9 (66.6%) French HNSCC patients have increased copy number [102]. PIK3CA mutation is generally less common than gene amplification. Somatic mutations, commonly including “hotspot” amino acid changes to the kinase (H1047R) or helical (E545K, E542K) domains, occur in 20.8% of the TCGA cohort, which is consistent with rates of ∼10-20% in other studies [95–97]. PIK3CA mutation rates greater than 10% were noted in cohorts from Thailand (6/58), India (2/19), and Israel (4/37) [96, 97, 100]. Surprisingly, a complete lack of PIK3CA mutations in the helical or kinase domains (exons 9 and 20) were observed in populations of 18 Vietnamese, 33 German, and 86 Greek patients as detected by PCR [97–99]. This may be due to increased activation of HRAS, which signals upstream of PIK3CA, in these epidemiologic sub-groups [103]. Due to the variation in PIK3CA mutation rates between 1/35 (2.9%) and 5/24 (20.8%) in US patient populations [95, 104] and the relatively small number of HNSCC tumor samples that have been sequenced worldwide, additional cohort studies are warranted to further consider potential associations between rates of genetic aberration and patient ethnicity or epidemiologic risk.


Genetic determinants in head and neck squamous cell carcinoma and their influence on global personalized medicine
Global variation in frequency of PIK3CA aberration in oral cancerFrequency of PIK3CA amplification (A) and mutation (B) in oral cancer cohorts from countries worldwide. Based on data from Murugan et al. [94] and review of more recent literature, as detailed in Table S2.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4979591&req=5

Figure 6: Global variation in frequency of PIK3CA aberration in oral cancerFrequency of PIK3CA amplification (A) and mutation (B) in oral cancer cohorts from countries worldwide. Based on data from Murugan et al. [94] and review of more recent literature, as detailed in Table S2.
Mentions: Rates of PIK3CA aberration have been assessed in various global cohorts [95–100] and are shown in Figure 6. Low frequencies of gene amplification were observed in 3/33 (9%) patients in a German HNSCC cohort as well as 3/115 (2.3%) and 6/50 (12%) individuals in two independent Japanese groups [96, 98, 101]. Alternatively, Redon et al. noted 6/9 (66.6%) French HNSCC patients have increased copy number [102]. PIK3CA mutation is generally less common than gene amplification. Somatic mutations, commonly including “hotspot” amino acid changes to the kinase (H1047R) or helical (E545K, E542K) domains, occur in 20.8% of the TCGA cohort, which is consistent with rates of ∼10-20% in other studies [95–97]. PIK3CA mutation rates greater than 10% were noted in cohorts from Thailand (6/58), India (2/19), and Israel (4/37) [96, 97, 100]. Surprisingly, a complete lack of PIK3CA mutations in the helical or kinase domains (exons 9 and 20) were observed in populations of 18 Vietnamese, 33 German, and 86 Greek patients as detected by PCR [97–99]. This may be due to increased activation of HRAS, which signals upstream of PIK3CA, in these epidemiologic sub-groups [103]. Due to the variation in PIK3CA mutation rates between 1/35 (2.9%) and 5/24 (20.8%) in US patient populations [95, 104] and the relatively small number of HNSCC tumor samples that have been sequenced worldwide, additional cohort studies are warranted to further consider potential associations between rates of genetic aberration and patient ethnicity or epidemiologic risk.

View Article: PubMed Central - PubMed

ABSTRACT

While sequencing studies have provided an improved understanding of the genetic landscape of head and neck squamous cell carcinomas (HNSCC), there remains a significant lack of genetic data derived from non-Caucasian cohorts. Additionally, there is wide variation in HNSCC incidence and mortality worldwide both between and within various geographic regions. These epidemiologic differences are in part accounted for by varying exposure to environmental risk factors such as tobacco, alcohol, high risk human papilloma viruses and betel quid. However, inherent genetic factors may also play an important role in this variability. As limited sequencing data is available for many populations, the involvement of unique genetic factors in HNSCC pathogenesis from epidemiologically diverse groups is unknown. Here, we review current knowledge about the epidemiologic, environmental, and genetic variation in HNSCC cohorts globally and discuss future studies necessary to further our understanding of these differences. Long-term, a more complete understanding of the genetic drivers found in diverse HNSCC cohorts may help the development of personalized medicine protocols for patients with rare or complex genetic events.

No MeSH data available.


Related in: MedlinePlus