Diagnosis, Differential ; Humans ; Lung Neoplasms/genetics* ; Neoplasm Metastasis ; Neoplasms, Multiple Primary/diagnosis*

OBJECTIVETo evaluate the frequency and nature of E-cadherin gene (CDH1) germline mutations in familial gastric cancer kindreds of china.

METHODSFive familial gastric cancer kindreds of Chinese origin were screened for germline CDH1 mutations, all of them meeting the clinical criteria for hereditary diffuse gastric cancer (HDGC), by PCR-DHPLC and direct sequencing.

RESULTSA new truncating mutation in exon 10 in B family was identified, producing a stop codon at position 503 (Q503X), resulting in a truncated protein. The proband of this family had metachronous development of lobular breast and diffuse type gastric carcinoma. No protein expression was detected in the lobular breast carcinoma, indicating complete inactivation of the gene.

CONCLUSIONSA Chinese gastric cancer family with CDH1 germline truncating mutation is described for the first time, and our findings suggest that lobular breast carcinoma might be part of the tumor spectrum of HDGC.

Adult ; Breast Neoplasms ; genetics ; Cadherins ; genetics ; Female ; Humans ; Male ; Middle Aged ; Mutation ; Neoplasms, Multiple Primary ; genetics ; Neoplastic Syndromes, Hereditary ; genetics ; Pedigree ; Polymerase Chain Reaction ; Stomach Neoplasms ; genetics

Animals ; CD40 Ligand ; genetics ; metabolism ; Carcinoma, Hepatocellular ; genetics ; metabolism ; therapy ; Genetic Therapy ; Liver Neoplasms ; genetics ; metabolism ; therapy ; Mice ; Neoplasms, Multiple Primary ; genetics ; metabolism ; therapy ; Transgenes ; genetics

Carcinoma, Hepatocellular ; genetics ; pathology ; secondary ; Diagnosis, Differential ; Humans ; Liver Neoplasms ; genetics ; pathology ; secondary ; Loss of Heterozygosity ; Male ; Microsatellite Repeats ; Middle Aged ; Neoplasms, Multiple Primary ; genetics

The rearrangement of the gene encoding the transcription factor ETS-related gene (ERG) is thought to play a key role in the development of prostate cancer. However, the studies on the ERG mutations have been rarely reported in non-small cell lung carcinoma (NSCLC). Here, we reported genetic features regarding a case of a 68-year-old male patient who presented the primary synchronous multiple tumor lesions in the separated lungs. The patient was hospitalized due to the presence of tumor lesions at the right and left lungs revealed by a chest computerized tomography (CT) scan. After conducting lobectomies at the both lungs, the tumor nodules were all removed, and the histological analysis suggested adenocarcinoma at the both tumor lesions. The patient was diagnosed with synchronous multiple primary lung cancer (SMPLC) based on Martini-Melamed criteria and American College of Chest Physicians practice guidelines. An exome analysis of 315 genes in the two tumor lesions and a non-tumor lesion was conducted by using Illumina Nextseq500 platform from each tumor region to decipher a potential evolutional progress of SMPLC. Single or pair-end reads were first mapped to a human genome reference and filtered based on the mapping quality score. The read depth was ≥ 1 000× and the depth of coverage was 95%. The data revealed a discordant epidermal growth factor receptor (EGFR) from the separate lungs; additionally, a high frequency of point mutation on exon 9 H310P of the ERG gene was detected at the both sites of the tumor lesions. This case showed that a potential role of the molecular features analysis from each tumor lesion might contribute to the understanding of the evolutional development of SMPLC. This study suggests that the same environment may contribute certain gene(s) mutations in the same sites in the early stages of polyclonal tumor origins; meanwhile the extensive studies on these genes may help us understand the evolution and progress of tumor clones.
Adenocarcinoma ; Aged ; Carcinoma, Non-Small-Cell Lung ; Humans ; Lung Neoplasms/genetics* ; Male ; Neoplasms, Multiple Primary/genetics* ; Point Mutation ; Transcriptional Regulator ERG

Carney complex is a multiple neoplasia syndrome, inherited in an autosomal dominant manner, that is characterized by lentigines, cardiac myxoma, and numerous endocrine and other tumors, including primary pigmented nodular adrenocortical disease. Here, we describe a typical case of Carney complex in a 27- year-old female who exhibited spotty skin pigmentation on the lips, oral mucosa, fingers, and toes and several manifestations of Cushing's syndrome due to primary pigmented nodular adrenocortical disease. She also had pituitary adenoma, breast tumor and thyroid nodule. Only a few cases of this disorder have been reported in the Korean literature. All of them, however, had only two components of Carney complex: composed of skin pigmentation and primary pigmented nodular adrenocortical disease. Therefore, the present case seems to be the first true case of Carney complex reported in Korea.
Adult ; Cushing Syndrome/*diagnosis ; Female ; Human ; Hyperpigmentation/diagnosis ; Magnetic Resonance Imaging ; Multiple Endocrine Neoplasia/diagnosis ; Myxoma/*diagnosis/genetics ; Neoplasms, Multiple Primary/*diagnosis ; Pituitary Neoplasms/*diagnosis ; Skin Neoplasms/*diagnosis/genetics ; Syndrome

OBJECTIVETo explore the prevalence, clinical features and prognosis of multiple primary neoplasms in patients with colorectal carcinoma (CRC).

METHODSData of colorectal cancer patients admitted to our hospital from June 1994 to June 2002 were analyzed retrospectively. Patients were divided into multiple-cancer group (MCG) and single- cancer group (SCG). Clinical features and prognosis were compared between two groups.

RESULTSThe incidence of multiple cancers was 7.4 % (83/ 1125). Forty- seven patients had multiple colorectal cancers metachronous CRC(S) in 12 and synchronous CRC(S) in 35. Thirty- six patients 5 patients with synchronous cancers had malignant tumors outside colorectal tract,12 of whom were gastric carcinomas. No significant differences were found between MCG and SCG regarding gender, onset age, Dukes stage and differentiation of index CRC. Cancer family history (P=0.002) and colorectal adenoma (P=0.036) were significantly more common in MCG than those in SCG. The local recurrence or distant metastasis in MCG was significantly higher than that in SCG (P=0.047), though there was no significant difference in survival between the two groups. Forty- one percent of index tumors were located in right colon in MCG, significantly higher than that in SCG (P=0.048). The secondary tumors were mainly adenoma cancerization in MCG.

CONCLUSIONCancer family history and colorectal adenoma seems to be at high risk for developing multiple cancers in CRC patients. Gastric cancer and colorectal adenoma cancerization were common secondary tumors of multiple primary neoplasms in patients with colorectal carcinoma.

Adenomatous Polyps ; genetics ; Adult ; Aged ; Colorectal Neoplasms ; diagnosis ; epidemiology ; pathology ; Female ; Humans ; Male ; Middle Aged ; Neoplasm Staging ; Neoplasms, Multiple Primary ; diagnosis ; epidemiology ; pathology ; Prognosis ; Retrospective Studies ; Risk Factors

BACKGROUNDIn China, esophageal squamous cell carcinoma (ESCC) and gastric cardia adenocarcinoma (GCA) share susceptibility loci, but different rates of multiple primary cancer and male/female ratio suggest the proportion of familial cancer is not equal.

METHODSThe percent of cases with a positive family history, median onset age, rate of multiple primary cancer, and male/female ratio associated with upper, middle, lower third ESCC and GCA were compared to reveal the proportion of familial cancer. The 7267 subjects analyzed constituted all ESCC and GCA cases in whom the cancer was resected with cure intention between 1970 and 1994 at the 4th Hospital of Hebei Medical University.

RESULTSA positive family history for cancer was most often associated with the multiple primary ESCC and/or GCA cases, e.g. with 42% of the males and 59% of the females. For upper, middle, lower third ESCC and GCA, the percent of cases with a positive family history decreased by 38.5%, 26.3%, 26.5%, and 11.2% in males (P < 0.000) and 25.0%, 22.3%, 23.9%, and 9.8% in females (P < 0.0001). Median onset age increased from 49, 52, 55, to 56 years old in males and from 50, 53, 55, to 56 years old in females ( both P < 0.0001) for upper, middle, lower third ESCC and GCA. Male/female ratio increased from 2.2, 2.1, 2.2, to 6.2:1 for upper, middle, lower third ESCC and GCA (P < 0.0001). For upper, middle, lower third ESCC and GCA, the percent of multiple primary cancers decreased from 21.2%, 2.3%, 2.2%, to 1.5% in males and from 14.3%, 2.4%, 3.4%, to 3.1% in females. The preponderance of males, smoking, drinking, or onset-age ≥ 50 years was significantly higher in GCA than in ESCC, and the difference in the rates of multiple primary cancers between the preponderant and the non-preponderant cases was significant in GCA, but not in ESCC, suggesting non-equal requirement for genetic susceptibility when environmental hazards did not exist.

CONCLUSIONSThe proportion of familial cancer in upper gastrointestinal carcinomas decreases by the primary site of upper, middle, lower third esophagus and gastric cardia. Considering familial and sporadic cancers differ in preventability, screening strategy and recurrence, our findings have basic and clinical implications.

Adenocarcinoma ; genetics ; Age of Onset ; Carcinoma, Squamous Cell ; genetics ; Cardia ; China ; Esophageal Neoplasms ; genetics ; Female ; Genetic Loci ; Genetic Predisposition to Disease ; Humans ; Male ; Middle Aged ; Neoplasms, Multiple Primary ; epidemiology ; Risk Factors ; Stomach Neoplasms ; genetics

BACKGROUND/AIMS: Microsatellite instability (MSI) plays a crucial role in gastrointestinal carcinogenesis. The aim of this study was to clarify whether MSI is a useful marker for predicting synchronous gastric and colorectal neoplasms. METHODS: Consecutive patients who underwent both esophagogastroduodenoscopy and colonoscopy before the resection of gastric or colorectal cancers were included. MSI was analyzed using two mononucleotide and three dinucleotide markers. RESULTS: In total, 434 gastric cancers (372 microsatellite stability [MSS], 21 low incidence of MSI [MSI-L], and 41 high incidence of MSI [MSI-H]) and 162 colorectal cancers (138 MSS, 9 MSI-L, and 15 MSI-H) were included. Patients with MSI gastric cancer had a higher prevalence of synchronous colorectal cancer, colorectal adenoma, and gastric adenoma than those with MSS gastric cancers (4.8% vs 0.5%, p=0.023; 11.3% vs 3.2%, p=0.011; 3.2% vs 1.2%, p=0.00, respectively). The prevalence of synchronous colorectal adenomas was highest in MSI-L gastric cancers (19.0%), compared with MSI-H (7.3%) or MSS (3.2%) gastric cancers (p=0.002). In addition, there were no significant differences in the prevalence rates of synchronous colorectal adenoma among the MSI-H (13.3%), MSI-L (11.1%), and MSS (12.3%) colorectal cancers (p=0.987). CONCLUSIONS: The presence of MSI in gastric cancer may be a predictor of synchronous gastric and colorectal neoplasms, whereas MSI in colorectal cancer is not a predictor of synchronous colorectal adenoma.
Adenoma/*genetics/surgery ; Aged ; Colonoscopy ; Colorectal Neoplasms/*genetics/surgery ; Endoscopy, Digestive System ; Female ; Humans ; Male ; *Microsatellite Instability ; Middle Aged ; Neoplasms, Multiple Primary/*genetics/surgery ; Predictive Value of Tests ; Stomach Neoplasms/*genetics/surgery

Adenocarcinoma, Mucinous ; chemistry ; genetics ; Female ; Gastrointestinal Stromal Tumors ; chemistry ; genetics ; Humans ; Middle Aged ; Mutation ; Neoplasms, Multiple Primary ; chemistry ; genetics ; Proto-Oncogene Proteins c-kit ; analysis ; Receptors, Platelet-Derived Growth Factor ; genetics ; Stomach Neoplasms ; chemistry ; genetics