Etiologic value of <i>p53</i> mutation spectra and differences with histology in lung cancers

Shimmyo, Takuo; Okada, Akira; Hashimoto, Takehisa; Kobayashi, Yasuhito; Miyagi, Youhei; Ishikawa, Yuichi; Nakagawa, Ken; Osada, Hiroaki; Tsuchiya, Eiju

doi:10.1111/j.1349-7006.2007.00686.x

Cited by 11 publications

(14 citation statements)

References 48 publications

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“…The combined approach of DHPLC and DNA sequencing analysis revealed that of the 105 cases, 1 (1%, 95% confidence interval 0.02-5.2) carried a deleterious TP53 frame shift mutation in exon 5, c.499-500delCA. This germ line mutation was previously reported as a somatic mutation in four other cancer types [28][29][30][31], but it is the first incidence of it occurring in the germ line (Table 1). It was found in a 28-year-old early-onset breast cancer patient of Punjabi ethnicity with no family history of breast or ovarian cancer.…”

Section: Resultsmentioning

confidence: 77%

“…This is the first report of this mutation being identified in the germ line. Previously, it was reported as a somatic mutation in four patients with other cancer types: a women from Kashmir valley (Indian part) diagnosed with esophageal squamous cell carcinoma at age 50 [31], a Japanese male diagnosed with adenocarcinoma of the lung at age 60 [28], a German women diagnosed with squamous cell carcinoma of larynx at age 46 [29] and a male patient from the US diagnosed with adenocarcinoma of the descending/sigmoid colon at 61 years of age [30].…”

Section: Discussionmentioning

confidence: 99%

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Prevalence of TP53 germ line mutations in young Pakistani breast cancer patients

et al. 2012

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Women from Pakistan and India are more often diagnosed with early-onset breast cancer than Caucasian women. Given that only 12% of Pakistani women diagnosed with breast cancer at or before 30 years of age have previously been shown to harbor germ line mutations in the breast cancer susceptibility genes BRCA1 and BRCA2, the genetic causes of the majority of early-onset cases are unexplained. Since germ line mutations in the tumor suppressor gene TP53 predispose women to early-onset breast cancer, we assessed the prevalence of TP53 mutations in 105 early-onset breast cancer patients from Pakistan, who had previously been found to be negative for BRCA1 and BRCA2 germ line mutations. The patient group included 67 women diagnosed with early-onset breast cancer at or before age 30 with no family history of breast or ovarian cancer (EO30NFH group) and 38 women diagnosed with breast cancer at or before age 40 with one or more first- or second-degree relatives with breast or ovarian cancer (EO40FH group). Mutation analysis of the complete TP53 coding region was performed using denaturing high-performance liquid chromatography analysis, followed by DNA sequencing of variant fragments. One deleterious mutation, c.499-500delCA in exon 5, was identified in the 105 breast cancer patients (1%). This mutation is novel in the germ line and has not been described in other populations. It was detected in a 28-year-old patient with no family history of breast or ovarian cancer. This mutation is rare as it was not detected in additional 157 recently recruited non-BRCA1 and non-BRCA2-associated early-onset breast cancer patients. Our findings show that TP53 mutations may account for a minimal portion of early-onset breast cancer in Pakistan.

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Section: Resultsmentioning

confidence: 77%

Section: Discussionmentioning

confidence: 99%

Prevalence of TP53 germ line mutations in young Pakistani breast cancer patients

et al. 2012

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“…Similarly, a number of studies have shown that TP53 gene mutations are more common in lung cancers from smokers than they are in lung cancers from never smokers, and, again, the G:C to T:A transversions predominate with a specificity towards CpG sites [14, 17, 23–25]. Thus, there is a strong “fingerprint” of tobacco carcinogens in the DNA of lung cancer [24, 26]. …”

Section: Introductionmentioning

confidence: 99%

Genetic Mutations Associated with Cigarette Smoking in Pancreatic Cancer

Blackford¹,

Parmigiani

Kensler³

et al. 2009

Cancer Research

117

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Cigarette smoking doubles the risk of pancreatic cancer, and smoking accounts for 20% to 25% of pancreatic cancers. The recent sequencing of the pancreatic cancer genome provides an unprecedented opportunity to identify mutational patterns associated with smoking. We previously sequenced >750 million bp DNA from 23,219 transcripts in 24 adenocarcinomas of the pancreas (discovery screen). In this previous study, the 39 genes that were mutated more than once in the discovery screen were sequenced in an additional 90 adenocarcinomas of the pancreas (validation screen). Here, we compared the somatic mutations in the cancers obtained from individuals who ever smoked cigarettes (n = 64) to the somatic mutations in the cancers obtained from individuals who never smoked cigarettes (n = 50). When adjusted for age and gender, analyses of the discovery screen revealed significantly more nonsynonymous mutations in the carcinomas obtained from ever smokers (mean, 53.1 mutations per tumor; SD, 27.9) than in the carcinomas obtained from never smokers (mean, 38.5; SD, 11.1; P = 0.04). The difference between smokers and nonsmokers was not driven by mutations in known driver genes in pancreatic cancer (KRAS, TP53, CDKN2A/p16, and SMAD4), but instead was predominantly observed in genes mutated at lower frequency. No differences were observed in mutations in carcinomas from the head versus tail of the gland. Pancreatic carcinomas from cigarette smokers harbor more mutations than do carcinomas from never smokers. The types and patterns of these mutations provide insight into the mechanisms by which cigarette smoking causes pancreatic cancer. [Cancer Res 2009;69(8):3681-8]

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“…In colon cancer, many p53 mutations are located in CpG-rich regions that have a significant proportion of transitions [27,28]. Cancerous lungs of smokers have revealed both transversions and transitions in p53 [29], which may in part be a result of the oxidants generated in tar and the RNS in smoke. In contrast, in the cancerous lungs of non-smokers transitions are more prominent, suggesting that inflammation favors transitions.…”

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confidence: 99%