Cancer predisposing germline mutations in patients (pts) with urothelial cancer (UC) of the renal pelvis (R-P), ureter (U) and bladder (B).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 4510-4510 ◽  
Author(s):  
Maria Isabel Carlo ◽  
Liying Zhang ◽  
Diana Mandelker ◽  
Joseph Vijai ◽  
Catharine Kline Cipolla ◽  
...  
Keyword(s):  
Gene Mutations ◽  
Germline Mutations ◽  
Germline Gene ◽  
Repair Pathway ◽  
Cancer Syndrome ◽  
Full Spectrum ◽  
Inherited Cancer ◽  
Hereditary Component ◽  
History Of ◽  
Inherited Cancer Syndrome

4510 Background: Urothelial cancers (UC) are suspected to have a substantial hereditary component, but other than highly penetrant genes such as those in mismatch-repair pathway (e.g. MSH2) typically associated with R-P/U primaries, heritable gene mutations have not been systematically studied. We sought to investigate the prevalence of known cancer pre-disposing germline mutations in pts with UC originating from all sites within the urinary tract. Methods: Pts with R-P, U and B primaries, unselected for suspicion of inherited cancer syndrome, were prospectively enrolled from medical oncology and urology clinics to a germline sequencing protocol from June 2016 to January 2017. Germline gene analysis was performed in a CLIA-certified lab using a next generation sequencing (NGS) platform (MSK-IMPACT) that analyzes tumor-normal DNA pairs. The germline gene panel consisted of 76 genes associated with hereditary cancer predisposition. Results: As of January 24, 2017, 101 pts have NGS results available, with median age 63 (31-87), 76% male, 24% female. Primary sites were B (67%), R-P/U (31%), or both (3%). 73% had organ-confined disease and 27% had metastases. 8% had early onset (≤45 yrs at diagnosis), 10% had a family history of UC, 25% had documented non-UC cancers. 25 pathogenic or likely pathogenic (P-LP) mutations were identified in 22 patients. P-LP mutations were present in 29% of pts with R-P/U primaries and 18% of pts with B primaries. 12 DNA damage response gene alterations were found (4 CHEK2, 3 BRCA1, 2 BRCA2, 1 ATM, 1 BRIP1, 1 NBN) and 8 in Lynch syndrome associated genes (5 MSH2, 2 MSH6, 1 MLH1). Other mutations include 2 APC, 1 TP53, and 1 FH. Notably 3 pts had 2 alterations each ( MSH6/ APC, BRCA2/ APC, BRCA1/ CHEK2). 9/22 pts with P-LP mutations did not meet American College of Medical Genetics criteria for genetic screening. Conclusions: 22% of UC pts had a germline mutation in a cancer-associated gene. There was an unexpectedly high frequency of pts with DNA-repair pathway mutations. Active accrual is ongoing to define the full spectrum of alterations. These results have profound implications for genetic counseling and screening and further studies are warranted.

E-cadherin germline mutations define an inherited cancer syndrome dominated by diffuse gastric cancer

1999 ◽  
Vol 14 (3) ◽  
pp. 249-255 ◽  
Author(s):  
Parry J. Guilford ◽  
Justin B.W. Hopkins ◽  
William M. Grady ◽  
Sanford D. Markowitz ◽  
Joseph Willis ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Germline Mutations ◽  
Diffuse Gastric Cancer ◽  
Cancer Syndrome ◽  
Inherited Cancer ◽  
Inherited Cancer Syndrome ◽  
E Cadherin

scholarly journals Surveillance of Individuals with a Family History of Pancreatic Cancer and Inherited Cancer Syndromes: A Strategy for Detecting Early Pancreatic Cancers

Diagnostics ◽  
2019 ◽  
Vol 9 (4) ◽  
pp. 169
Author(s):  
Matsubayashi ◽  
Kiyozumi ◽  
Ishiwatari ◽  
Uesaka ◽  
Kikuyama ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Family History ◽  
Early Stage ◽  
Developed Countries ◽  
Familial Pancreatic Cancer ◽  
Cancer Syndrome ◽  
Inherited Cancer ◽  
Clinicopathological Findings ◽  
History Of ◽  
Cancer Syndromes

A family history of pancreatic cancer (PC) is a risk factor of PC, and risk levels increase as affected families grow in number and/or develop PC at younger ages. Familial pancreatic cancer (FPC) is defined as a client having at least two PC cases in a first degree relatives. In the narrow sense, FPC does not include some inherited cancer syndromes that are known to increase the risks of PC, such as Peutz–Jeghers syndrome (PJS), hereditary pancreatitis (HP), hereditary breast ovarian cancer syndrome (HBOC), and so on. FPC accounts for 5%–10% of total PC diagnoses and is marked by several features in genetic, epidemiological, and clinicopathological findings that are similar to or distinct from conventional PC. Recent advances in genetic medicine have led to an increased ability to identify germline variants of cancer-associated genes. To date, high-risk individuals (HRIs) in many developed countries, including FPC kindreds and inherited cancer syndromes, are screened clinically to detect and treat early-stage PC. This article highlights the concept of FPC and the most recent data on its detection.

The Predisposing Gene of the Eker Rat Inherited Cancer Syndrome Is Tightly Linked to the Tuberous Sclerosis (TSC2) Gene

1994 ◽  
Vol 203 (2) ◽  
pp. 1302-1308 ◽  
Author(s):  
O. Hino ◽  
T. Kobayashi ◽  
H. Tsuchiya ◽  
Y. Kikuchi ◽  
E. Kobayashi ◽  
...  
Keyword(s):  
Tuberous Sclerosis ◽  
Tsc2 Gene ◽  
Cancer Syndrome ◽  
Inherited Cancer ◽  
Eker Rat ◽  
Inherited Cancer Syndrome

scholarly journals Familial/inherited cancer syndrome: a focus on the highly consanguineous Arab population

2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Fawz S. AlHarthi ◽  
Alya Qari ◽  
Alaa Edress ◽  
Malak Abedalthagafi
Keyword(s):  
Cancer Syndrome ◽  
Arab Population ◽  
Inherited Cancer ◽  
Inherited Cancer Syndrome

scholarly journals Hereditary Diffuse Gastric Cancer: Multidisciplinary Case Report with Review of the Literature

2011 ◽  
Vol 2011 ◽  
pp. 1-5 ◽  
Author(s):  
Rebecca Wilcox ◽  
Melody Perpich ◽  
Amy Noffsinger ◽  
Mitchell C. Posner ◽  
Kumarasen Cooper
Keyword(s):  
Gastric Cancer ◽  
Case Report ◽  
Hereditary Diffuse Gastric Cancer ◽  
Diffuse Gastric Cancer ◽  
Review Of The Literature ◽  
Cancer Syndrome ◽  
Inherited Cancer ◽  
Prophylactic Gastrectomy ◽  
Signet Ring ◽  
Inherited Cancer Syndrome

Hereditary diffuse gastric cancer (HDGC) is a rare, inherited cancer syndrome with at least one fourth of HDGC patients having an autosomal dominantly inherited mutation of CDH1 (E-Cadherin). Penetrance is relatively high (70–80% lifetime risk for gastric cancer). It is important for pathologists to recognize the syndrome's phenotype in early gastric lesions: patchy intramucosal signet ring cells often associated with pagetoid spread. Due to the insidious nature of this lesion, surveillance is limited and currently prophylactic gastrectomy is an option chosen by many HDGC patients. We present a case report from a multidisciplinary team of authors with a review of the literature that includes the updated guidelines for CDH1 genetic testing.

Cowden’s syndrome

2011 ◽  
pp. 980-986
Author(s):  
Charis Eng
Keyword(s):  
Thyroid Cancer ◽  
Susceptibility Gene ◽  
Multinodular Goitre ◽  
Cancer Syndrome ◽  
Inherited Cancer ◽  
Organ Systems ◽  
Cowden’S Syndrome ◽  
Thyroid Adenomas ◽  
Cell Layers ◽  
Inherited Cancer Syndrome

Cowden’s syndrome (OMIM 158350), named after Rachel Cowden, is an autosomal dominant inherited cancer syndrome characterized by multiple hamartomas involving organ systems derived from all three germ cell layers and a risk of breast and thyroid cancers (1, 2). Endocrinologists may make the diagnosis of Cowden’s syndrome when they are presented with these patients’ endocrine lesions, chief of which are multinodular goitre, thyroid adenomas, and epithelial thyroid cancer. The Cowden’s syndrome susceptibility gene, PTEN, is located on chromosome sub-band 10q23.3 (3, 4).

Discovery and prevalence of cancer-susceptibility germline mutations (Mts) in patients (Pts) with advanced renal cell carcinoma (aRCC).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 4524-4524 ◽  
Author(s):  
Maria Isabel Carlo ◽  
Semanti Mukherjee ◽  
Yelena Kemel ◽  
Liying Zhang ◽  
Diana Mandelker ◽  
...  
Keyword(s):  
Family History ◽  
Early Onset ◽  
Cancer Susceptibility ◽  
Cancer Syndrome ◽  
Exact Test ◽  
Sequencing Platform ◽  
Clinical Criteria ◽  
Inherited Cancer ◽  
Increased Risk ◽  
Inherited Cancer Syndrome

4524 Background: About 5% of RCC is thought to be familial, but recent studies suggest this may be an underestimate (Int. J. Cancer;100:476). We studied the prevalence of germline cancer-susceptibility mts in pts with aRCC. Methods: Pts with aRCC (stage III or IV), unselected for suspicion of an inherited cancer syndrome, were offered germline testing for 76 cancer-associated genes between 10/2015 and 12/2016. Germline sequencing was done as part of MSK-IMPACT, a matched tumor-normal next-generation sequencing platform. Results: 203/213 pts accepted testing (median age 55, range 13-55) of whom 73% had clear cell RCC (ccRCC), 92% had metastases, 20% were early onset (≤46 yrs at diagnosis), 9% had a family history of RCC, 6% multifocal RCC at diagnosis, and 15% ≥2 primary malignancies. Pathogenic/likely pathogenic mts were found in 35 pts (17%): 12 (6%) with mts in genes associated with familial RCC; 10 (5%) mts in high/moderate penetrance genes not linked to RCC (Table).13 (6%) had mts in genes of low/uncertain penetrance or for autosomal recessive disease. Mts were present in 15% of ccRCC and 19% of non-ccRCC. Mts were not more common in pts with early onset, family history, multifocal RCC, or ≥2 malignancies (p>0.1 for each by Fisher’s exact test). Notably, 4/12 pts with mts in familial RCC genes did not meet the American College of Medical Genetics (ACMG) criteria for testing (1 each VHL, BAP1, SDHA, FH). Prevalence of CHEK2 mts was compared to population databases (ExAC); CHEK2 conferred a relative risk of 10.9 (p< 0. 002; CI=3.9-24.7) for RCC. Conclusions: 17% of aRCC pts had a germline mutation in a cancer-associated gene of which 33% of the high penetrance RCC germline mts were not identified using standard clinical criteria, providing rationale for broad testing. Once the increased risk is confirmed, CHEK2 should be included in RCC genetic testing. [Table: see text]

Clinical characterization of pancreatic ductal adenocarcinomas (PDAC) with mismatch repair (MMR) gene mutations.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15791-e15791 ◽  
Author(s):  
Zishuo Ian Hu ◽  
Anna M. Varghese ◽  
Jinru Shia ◽  
Alice Zervoudakis ◽  
Maeve Aine Lowery ◽  
...  
Keyword(s):  
Mismatch Repair ◽  
Somatic Mutations ◽  
Gene Mutations ◽  
Germline Mutations ◽  
Cancer Center ◽  
Mmr Genes ◽  
Mutational Burden ◽  
Repair Deficiency ◽  
History Of

e15791 Background: Tumors with mismatch repair-deficiency (MMRD) have a high mutational burden and have good responses to immunotherapy (Le, NEJM, 2015). We describe the natural course, clinicopathological, and genomic status of MMRD PDAC patients (pts) at Memorial Sloan Kettering Cancer Center (MSKCC). Methods: MSKCC institutional registry and ICD billing database queried from 2006-2016 for PDAC pts with genetically confirmed mutations in mismatch repair (MMR) genes. Mutation # determined via MSK-IMPACT, a targeted tumor next generation sequencing (NGS) test (Cheng, J Mol Diagn, 2015). Results: 5/607 (0.8%) PDAC pts had Lynch syndrome (LS) (confirmed germline mutations) (Table 1). Of the 5 LS pts, all had > 10 mutations in NGS, with 4 of 5 having > 50 mutations. 4 of 5 (80%) are alive at last follow-up (survival 30-314 months). N=4 had extensive personal/family history of cancer. Of N=3 who had resected disease, all 3 had recurrence at 11, 49 and 311 months, and all are alive (survival: 69-314 months). Of N= 2 pts that had unresectable tumors, one passed away at 30 months while the other is on checkpoint inhibitor trial and is alive at 30 months. In contrast, 7/607 (1.1%) PDAC pts had somatic mutations in MMR genes with an average of 5.7 mutations in NGS, with 4/7 having <5 mutations. 4/7 (57%) are deceased at last follow-up (survival: 10-42 months). Conclusions: All cases with germline mutations in the MMR genes, with one exception, had high mutation #. All cases with somatic mutations in the MMR genes had low mutation #. Germline mutations in MMR genes and high mutational burden may predict for a prognostically favorable subgroup of PDAC pts with high susceptibility to immune oncology agents. [Table: see text]

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