Molecular pathology of lung cancer: key to personalized medicine

Liu, Cheng; Alexander, Riley E.; MacLennan, Gregory T.; Cummings, Oscar W.; Montironi, Rodolfo; López-Beltrán, Antonio; Cramer, Harvey; Davidson, Darrell D.; Zhang, Shaobo

doi:10.1038/modpathol.2011.215

Cited by 218 publications

(198 citation statements)

References 240 publications

(375 reference statements)

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“…Point mutations in exon 18 (G719A, G719S, and G719C) have been described in about 1% of those patients. Less-frequent EGFR mutations underlying drug sensitivity or resistance have been described elsewhere [16,17].…”

Section: Glossarymentioning

confidence: 99%

EGFR and NF-κB: partners in cancer

Shostak

Chariot

2015

Trends in Molecular Medicine

190

160

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Section: Glossarymentioning

confidence: 99%

EGFR and NF-κB: partners in cancer

Shostak

Chariot

2015

Trends in Molecular Medicine

190

160

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“…13,17 However, the mutational events tested in this study are those most strongly associated with prediction to targeted therapies in lung adenocarcinoma and, as such, were the only ones examined. 13,34 In addition, we chose to not evaluate EGFR expression by immunohistochemistry. This has been reported to be a poor predictor of response to therapy in lung adenocarcinoma and is seen to lack correlation with EGFR mutations.…”

Section: Discussionmentioning

confidence: 90%

“…These parameters are consistent with methods used in studies examining both EGFR and ALK in lung adenocarcinoma. 13,[27][28][29] …”

Section: Fluorescence In Situ Hybridizationmentioning

confidence: 99%

“…[12][13][14][15] Therapies targeting the mutant EGFR have allowed for new and more personalized treatment options in these cancers. [16][17][18] Rearrangements involving anaplastic lymphoma kinase (ALK), most notably the EML4-ALK rearrangement, have shown considerable clinical utility in the treatment of certain lung cancers.…”

mentioning

confidence: 99%

“…[16][17][18] Rearrangements involving anaplastic lymphoma kinase (ALK), most notably the EML4-ALK rearrangement, have shown considerable clinical utility in the treatment of certain lung cancers. 13,17,[19][20][21] Although currently less specific and less predictive of therapeutic results, the detection of EGFR polysomy has been seen in many tumors to correlate with tumor activity and infers a role of EGFR in the propagation of tumors. [22][23][24][25] The goal of this study was to determine whether EGFR mutations, EGFR polysomy, or ALK rearrangements are present in primary adenocarcinoma of the urinary bladder as they may provide therapeutic targets in this disease.…”

mentioning

confidence: 99%

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EGFR alterations and EML4-ALK rearrangement in primary adenocarcinoma of the urinary bladder

et al. 2014

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The identification of mutations in epidermal growth factor receptor (EGFR) and translocations involving anaplastic lymphoma kinase (ALK) in lung adenocarcinoma has drastically changed understanding of the disease and led to the development of targeted therapies. Adenocarcinoma of the urinary bladder is rare and poorly understood at the molecular level. We undertook this study to determine whether EGFR mutations, increases in EGFR copy number, or ALK translocations are present in these tumors. Twenty-eight cases of primary bladder adenocarcinoma were analyzed. For EGFR mutational analysis, PCR-amplified products were analyzed on the Q24 Pyrosequencer with Qiagen EGFR Pyro Kits. All cases were analyzed via fluorescence in situ hybridization (FISH) using Vysis ALK Break Apart FISH Probes for detection of ALK chromosomal translocation and Vysis Dual Color Probes to assess for increased gene copy number of EGFR. None of the 28 cases examined showed mutational events in EGFR or ALK rearrangements. EGFR polysomy was seen in 10 out of 28 (36%) cases. No correlation with EGFR polysomy was seen in the tumors with respect to age, histologic subtypes, pathologic stage, or lymph node metastasis. In summary, EGFR mutations and ALK rearrangements do not appear to be involved in the development of primary adenocarcinoma of the urinary bladder. A subgroup of cases (36%), however, demonstrated increased gene copy number of EGFR by FISH.

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Two BRM promoter insertion polymorphisms increase the risk of early‐stage upper aerodigestive tract cancers

et al. 2014

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Brahma (BRM) has a key function in chromatin remodeling. Two germline BRM promoter insertion–deletion polymorphisms, BRM-741 and BRM-1321, have been previously associated with an increased risk of lung cancer in smokers and head and neck cancer. To further evaluate their role in cancer susceptibility particularly in early disease, we conducted a preplanned case–control study to investigate the association between the BRM promoter variants and stage I/II upper aerodigestive tract (UADT) cancers (i.e., lung, esophageal, head and neck), a group of early-stage malignancies in which molecular and genetic etiologic factors are poorly understood. The effects of various clinical factors on this association were also studied. We analyzed 562 cases of early-stage UADT cancers and 993 matched healthy controls. The double homozygous BRM promoter variants were associated with a significantly increased risk of early stage UADT cancers (adjusted odds ratio [aOR], 2.46; 95% confidence interval [CI], 1.7–3.8). This association was observed in lung (aOR, 2.61; 95% CI, 1.5–4.9) and head and neck (aOR, 2.75; 95% CI, 1.4–5.6) cancers, but not significantly in esophageal cancer (aOR, 1.66; 95% CI, 0.7–5.8). There was a nonsignificant trend for increased risk in the heterozygotes or single homozygotes. The relationship between the BRM polymorphisms and early-stage UADT cancers was independent of age, sex, smoking status, histology, and clinical stage. These findings suggest that the BRM promoter double insertion homozygotes may be associated with an increased risk of early-stage UADT cancers independent of smoking status and histology, which must be further validated in other populations.

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Molecular pathology of lung cancer: key to personalized medicine

Cited by 218 publications

References 240 publications

EGFR and NF-κB: partners in cancer

EGFR and NF-κB: partners in cancer

EGFR alterations and EML4-ALK rearrangement in primary adenocarcinoma of the urinary bladder

Two BRM promoter insertion polymorphisms increase the risk of early‐stage upper aerodigestive tract cancers

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