Over the past decade, comprehensive sequencing efforts have revealed the genomic landscapes of common forms of human cancer. For most cancer types, this landscape consists of a small number of “mountains” (genes altered in a high percentage of tumors) and a much larger number of “hills” (genes altered infrequently). To date, these studies have revealed ~140 genes that, when altered by intragenic mutations, can promote or “drive” tumorigenesis. A typical tumor contains two to eight of these “driver gene” mutations; the remaining mutations are passengers that confer no selective growth advantage. Driver genes can be classified into 12 signaling pathways that regulate three core cellular processes: cell fate, cell survival, and genome maintenance. A better understanding of these pathways is one of the most pressing needs in basic cancer research. Even now, however, our knowledge of cancer genomes is sufficient to guide the development of more effective approaches for reducing cancer morbidity and mortality.

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Cancer Genome Landscapes

The Cancer Genome Atlas (TCGA) Research Network has profiled and analyzed large numbers of human tumors to discover molecular aberrations at the DNA, RNA, protein and epigenetic levels. The resulting rich data provide a major opportunity to develop an integrated picture of commonalities, differences and emergent themes across tumor lineages. The Pan-Cancer initiative compares the first 12 tumor types profiled by TCGA. Analysis of the molecular aberrations and their functional roles across tumor types will teach us how to extend therapies effective in one cancer type to others with a similar genomic profile.

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The cancer genome atlas pan-cancer analysis project

The Cancer Genome Atlas Pan-Cancer analysis project

Background Oncogenic fusion genes consisting of EML4 and anaplastic lymphoma kinase (ALK) are present in a subgroup of non–small-cell lung cancers, representing 2 to 7% of such tumors. We explored the therapeutic efficacy of inhibiting ALK in such tumors in an early-phase clinical trial of crizotinib (PF-02341066), an orally available small-molecule inhibitor of the ALK tyrosine kinase. Methods After screening tumor samples from approximately 1500 patients with non–small-cell lung cancer for the presence of ALK rearrangements, we identified 82 patients with advanced ALK-positive disease who were eligible for the clinical trial. Most of the patients had received previous treatment. These patients were enrolled in an expanded cohort study instituted after phase 1 dose escalation had established a recommended crizotinib dose of 250 mg twice daily in 28-day cycles. Patients were assessed for adverse events and response to therapy. Results Patients with ALK rearrangements tended to be younger than those without the rearrangements, and most of the patients had little or no exposure to tobacco and had adenocarcinomas. At a mean treatment duration of 6.4 months, the overall response rate was 57% (47 of 82 patients, with 46 confirmed partial responses and 1 confirmed complete response); 27 patients (33%) had stable disease. A total of 63 of 82 patients (77%) were continuing to receive crizotinib at the time of data cutoff, and the estimated probability of 6-month progression-free survival was 72%, with no median for the study reached. The drug resulted in grade 1 or 2 (mild) gastrointestinal side effects. Conclusions The inhibition of ALK in lung tumors with the ALK rearrangement resulted in tumor shrinkage or stable disease in most patients. (Funded by Pfizer and others; ClinicalTrials.gov number, NCT00585195.)

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Anaplastic Lymphoma Kinase Inhibition in Non–Small-Cell Lung Cancer

https://www.hal.inserm.fr/inserm-00561753/document

International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society International Multidisciplinary Classification of Lung Adenocarcinoma

Pleural perforation of a saprophytic aspergilloma secondary to blunt chest trauma.

We report a case of a metastatic lung tumor from an occult thyroid oncocytic carcinoma, growing into the bronchial lumen. A 70-year-old woman was referred to our hospital because of abnormal shadows which had been increasing in size for 4 years, in the chest radiograph. Bronchoscopy revealed an endobronchial tumor at the orifice of the left B4b. Histological and immunohistological examination of the lesion showed tumor cells with immunoreactivity for thyroglobulin, and a metastatic oncocytic carcinoma from the thyroid was diagnosed. Closer examination of the neck revealed thyroid carcinoma, and total thyroidectomy was performed. Endobronchial metastasis of thyroid oncocytic carcinoma is very rare. In this case, immunohistological examination was useful for detecting the primary site.

A case of metastatic lung tumor from an occult thyroid oncocytic carcinoma growing into the bronchial lumen

症例は57歳, 男性.血液検査上CEAが経時的に異常上昇したため (術前150ng/ml), 胸部CTで認められた右上葉の肺嚢胞壁の硬結性病変を悪性と疑い開胸生検術を施行した.肺尖部の巨大肺嚢胞壁の肺門側に径2cm大の搬痕様の腺癌を認めた.病変は奇静脈, 右迷走神経を巻き込み肋間胸壁に浸潤していた.胸壁, 奇静脈, 迷走神経を合併切除し, 右肺上葉切除, 縦隔リンパ節郭清術を施行した.組織診では, 右肺上葉の嚢胞壁に発生したCEA産生能の高い低分化腺癌で, 病期P-T3N2M0のIIIAと診断した.術後CEA値は著明に減少し, 化学療法2クール施行後正常域になった.CEA値が10ng/mlを超えるとき, 肺嚢胞壁に肥厚性病変がみられるときには, 肺癌を念頭において積極的に診断治療すべきと思われた.

Primary lung cancer contiguous with a giant bulla diagnosed by marked increased plasma level of carcinoembryonic antigen (CEA); report of a case

症例1は, 61歳, 女性. 眼サルコイドーシスを疑われ, TBLBにて組織診行い, サルコイドーシスの確定診断を得た. その時点の胸部X線写真にて右上肺野に陰影があり, 次第にその陰影が増大してきたため初診より6年後, TBLB施行, 肺癌と診断され, 右上葉切除術施行. 病理組織学的に腺癌, 細気管支肺胞型腺癌と診断され, 所属リンパ節はすべてサルコイドーシスに一致する非乾酪性類上皮細胞肉芽腫で占められ, 転移を認めなかった.症例2.73歳, 男性. 検診異常にて精査. 肺癌の診断を得る.4年前の胸部X線写真にて肺癌と診断された部位に陰影がみられ, かつBHLも認められた. 右下葉切除術を行い, 組織型は腺癌, 乳頭状癌であった. 所属リンパ節は高度に腫大していたが, 転移を認めず, 無数の非乾酪性類上皮細胞肉芽腫が認められた. サルコイドーシスに肺癌の合併することは稀であるがこの2症例のように, 長期にわたりサルコイドーシスと肺癌の共存した例は少なく, 両疾患の合併機序を解明するに際し興味ある症例と思われた.

Two Cases of Resected Lung Cancer Complicated with Sarcoidosis.

右上葉気管支内腔に限局し, 充満性に発育した腎癌の転移性気道腫瘍に対し右上葉管状切除術を施行した1例を報告する.症例は, 53歳男性で, 喀血, 腫瘤の喀出を主訴に外来受診した.既往歴では, 8年前に左腎癌にて腎摘出術を行なっていた.気管支鏡では, 疣贅状の腫瘤が右上幹入口部を完全に閉塞し, 一部主幹に突出していた.喀出した腫瘤の組織診で, 腎癌の転移性気道腫瘍と診断した.全身検索の結果, 局所再発, 多臓器転移を認めず右肺上葉管状切除術, 縦隔リンパ節郭清を施行した.病理組織では, clear cell carcinomaが右B1, B2の気管支内腔に限局し, 充満するように発育していた.術後5年再発徴候は認められない.転移性気道腫瘍としては, 腎癌は多く報告されているが本例の如く, 肺実質内への侵襲がなく気道内腔に広汎に発育した特異な転移形式を認めた症例は珍しく文献的考察を加え報告する.

Yasunori Sohara

Papers

Pleural perforation of a saprophytic aspergilloma secondary to blunt chest trauma.

A case of metastatic lung tumor from an occult thyroid oncocytic carcinoma growing into the bronchial lumen

Primary lung cancer contiguous with a giant bulla diagnosed by marked increased plasma level of carcinoembryonic antigen (CEA); report of a case

Two Cases of Resected Lung Cancer Complicated with Sarcoidosis.

A unique endobronchial metastasis of a renal cell carcinoma; report of a case