Missense Mismatch Repair Gene Alterations, Microsatellite Instability, and Hereditary Nonpolyposis Colorectal Cancer

2002 ◽  
Vol 20 (14) ◽  
pp. 3178-3179 ◽  
Author(s):  
Wade S. Samowitz ◽  
Martha L. Slattery ◽  
Emilio Porfiri ◽  
Mario Scartozzi ◽  
Andrea Piga ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Microsatellite Instability ◽  
Mismatch Repair ◽  
Hereditary Nonpolyposis Colorectal Cancer ◽  
Mismatch Repair Gene ◽  
Repair Gene ◽  
Hereditary Nonpolyposis ◽  
Gene Alterations

Immunohistochemistry Identifies Carriers of Mismatch Repair Gene Defects Causing Hereditary Nonpolyposis Colorectal Cancer

2005 ◽  
Vol 23 (21) ◽  
pp. 4705-4712 ◽  
Author(s):  
Astrid T. Stormorken ◽  
Inger Marie Bowitz-Lothe ◽  
Tove Norèn ◽  
Elin Kure ◽  
Steinar Aase ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Mismatch Repair ◽  
Hereditary Nonpolyposis Colorectal Cancer ◽  
Mismatch Repair Gene ◽  
Repair Gene ◽  
Predictive Values ◽  
Blood Samples ◽  
Bethesda Criteria ◽  
Amsterdam Criteria ◽  
Hereditary Nonpolyposis

Purpose Hereditary nonpolyposis colorectal cancer (HNPCC) may be caused by mutations in mismatch repair (MMR) genes. The aim of this study was to validate immunohistochemistry and family history as prescreening tools to predict germline mutations in MLH1, MSH2, and MSH6. Patients and Methods Pedigrees from 250 families were extended, cancer diagnoses were verified, and families were classified according to the Amsterdam and the Bethesda criteria. Tumor specimens were examined with immunohistochemistry for the presence of MLH1, MSH2, and MSH6 proteins. Mutation analyses were performed in blood samples from the same patients. Results Blood samples from affected index persons in 181 families and tumor specimens from 127 of the affected index persons were obtained. Thirty tumors lacked one or more gene products. Sensitivity of immunohistochemistry to detect mutation carriers was 100%, specificity was 82%, and positive predictive value was 85%. Sensitivities, specificities, and positive predictive values for the Amsterdam criteria were 82%, 8%, and 45%, respectively, and for the Bethesda criteria were 100%, 0%, and 48%, respectively. Distribution of mutations was MLH1 = 4, MSH2 = 11, and MSH6 = 4. Conclusion Wide clinical criteria to select HNPCC kindreds, followed by immunohistochemistry of tumor material from one affected person in each family, had high sensitivity and specificity to predict MMR mutations.

Genetic profiles of hereditary nonpolyposis colorectal cancer.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 469-469
Author(s):  
C. Therklidsen ◽  
G. Jonsson ◽  
I. Bernstein ◽  
M. Nilbert
Keyword(s):  
Colorectal Cancer ◽  
Mismatch Repair ◽  
Hereditary Nonpolyposis Colorectal Cancer ◽  
Gene Mutations ◽  
Comparative Genomic ◽  
Mismatch Repair Gene ◽  
Repair Gene ◽  
Hereditary Nonpolyposis ◽  
Gains And Losses ◽  
Mismatch Repair Gene Mutations

469 Background: With the aim to identify genetic markers of hereditary nonpolyposis colorectal cancer (HNPCC), we applied tiling BAC array-based comparative genomic hybridization (aCGH) to 46 HNPCC-associated colorectal cancer. Methods: 32 k iling BAC arrays were used to generate high-density genomic profiles. Tumors were selected through a case-control design with half of the tumors derived from individuals with disease-predisposing mismatch repair gene mutations and the reminder from phenotypic HNPCC families without identified mutations. In addition, an equal number of sporadic tumors were used for comparison. Results: Tumors with disease-predisposing germline mutations showed frequent gains of chromosomes 1p (39%), 17 (43%), 19 (57%) and 22q (30%). HNPCC associated tumors without mutations did as a group have more complex alterations with the most frequent changes being gains of 20q (70%), 19 (35%), 17 (26%) and loss of 18 (39%). Gains of 1p and 20q and loss of chromosome 18 were identified as significant discriminators between HNPCC tumors with/without germline MMR gene mutations. Conclusions: The aCGH profiles of HNPCC-associated colorectal cancer suggest that specific gains and losses may be used to distinguish between tumors with/without germline mismatch repair gene mutations. No significant financial relationships to disclose.

Mismatch repair gene alteration subtypes impact age of onset of mismatch repair-deficient cancers.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 10521-10521
Author(s):  
Aifen Wang ◽  
Weidong Hu ◽  
Ninghan Feng ◽  
Yong Yin ◽  
Zhe Pei
Keyword(s):  
Prostate Cancer ◽  
Colorectal Cancer ◽  
Mismatch Repair ◽  
Age Of Onset ◽  
Age At Onset ◽  
Mismatch Repair Gene ◽  
Repair Gene ◽  
Ovarian Cancers ◽  
Age Range ◽  
Gene Alterations

10521 Background: This study investigated whether mismatch repair (MMR) gene alterations and alteration subtypes impacted age at onset of MMR-deficient cancers. Methods: A retrospective study of association of MMR-deficient alterations and age of onset of MMR-deficient lung, breast, prostate, bladder, colorectal, endometrial, and/or ovarian cancers was conducted by using cBIPORTAL dataset. Results: A total of 815 participants with MMR-deficient alterations were enrolled, 346 males and 469 females (median age 63 years; age range, 20-90 years). Males were diagnosed as colorectal and bladder cancer at later ages than females. When stratified by alteration type, individuals with MSH6 or PMS2 missense alterations had later ages of onset of colorectal cancer than those with no missense alterations. Participants with MSH2 AMP alterations were older at the diagnosis of endometrial cancer than those without MSH2 AMP alterations. Females with MLH1 missense alterations had later ages of onset of ovarian cancer than those with no missense alterations. Individuals with PMS2 AMP alterations were confirmed with lung cancer at later ages than those with no PMS2 AMP alterations. Carriers with MSH6or PMS2 missense alterations were older at the time of diagnosis of prostate cancer than those with no missense alterations. Conclusions: Gene alterations and subtype of alterations could stratify carriers with MMR-deficiency in bespoke surveillance. The mechanism of the association of MMR-deficient alterations and alteration subtypes and age at the diagnosis of MMR-deficient cancers needs to be further study.[Table: see text]

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